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Sample records for chromosomal region xp22

  1. Localization of a new type of X-linked liver glycogenosis to the chromosomal region Xp22 containing the liver {alpha}-subunit of phosphorylase kinase (PHKA2)

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    Hendrickx, J.; Coucke, P.; Willems, P.J. [Univ. of Antwerp (Belgium)] [and others

    1994-06-01

    The authors describe here a new type of X-linked liver glycogen storage disease. The main symptoms include liver enlargement and growth retardation. The clinical and biochemical abnormalities of this glycogenosis are similar to those of classical X-linked liver glycogenosis due to phosphorylase kinase deficiency (XLG). However, in constrast to patients with XLG, the patients described here have no reduced phosphorylase kinase activity in erythrocytes and leukocytes, and no enzyme deficiency could be found. Linkage analysis of four families with this X-linked type of liver glycogenosis assigned the disease gene to Xp22. Lod scores obtained with the markers DXS987, DXS207, and DXS999 were 3.97, 2.71, and 2.40, respectively, all at 0% recombination. Multipoint linkage analysis localized the disease gene between DXS143 and DXS989 with a maximum lod score of 4.70 at {theta}=0, relative to DXS987. As both the classical XLG gene and the liver {alpha}-subunit of PHK (PHKA2) are also located in Xp22, this variant type of XLG may be allelic to classical XLG, and both diseases may be caused by mutations in PHKA2. Therefore, they propose to classify XLG as XLG type I (the classical type of XLG) and XLG type II (the variant type of XLG). 28 refs., 2 figs., 3 tabs.

  2. [X-chromosome-linked ichthyosis associated to epilepsy, hyperactivity, autism and mental retardation, due to the Xp22.31 microdeletion].

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    Carrascosa-Romero, M Carmen; Suela, Javier; Alfaro-Ponce, Blanca; Cepillo-Boluda, Antonio J

    2012-02-16

    X-chromosome-linked ichthyosis is caused by mutation or deletion of the STS gene associated with a deficiency of the enzyme steroid sulphatase, located in the distal part of the short arm of the X chromosome (Xp22.3-pter), close to the pseudo-autosomal region. Depending on its size, it can present as an isolated entity or combined with a syndrome caused by neighbouring genes, thus associating itself with other monogenic diseases as well as other mental disorders. The most relevant findings from the literature review are the importance of the Xp22.3-pter region and the higher incidence of neurological disorders among males (attention deficit hyperactivity disorder, autism and X-linked mental retardation). The role and implication of these genes in the disease are discussed and the authors suggest a possible contribution of the gene PNPLA4, which was originally described as GS2 and codes for calcium-independent phospholipase A2 beta, involved in lipoprotein metabolism, as one of the causes of autism. Improvements have been observed following treatment with citicoline, thanks to the role this nootropic plays in the biosynthesis of structural phospholipids involved in the formation and repair of the neuronal membrane.

  3. Schizophrenia susceptibility gene locus at Xp22.3.

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    Milunsky, J; Huang, X L; Wyandt, H E; Milunsky, A

    1999-06-01

    Multiple genetic loci have been implicated in the search for schizophrenia susceptibility genes, none having been proven as causal. Genetic heterogeneity is probable in the polygenic etiology of schizophrenia. We report on two unrelated Caucasian women with paranoid schizophrenia (meeting Diagnostic and Statistical Manual of Mental Disorders (DSM IV) criteria) who have an Xp22.3 overlapping deletion characterized by fluorescence in situ hybridization (FISH). Patient 1 was previously reported by us (Wyandt HE, Bugeau-Michaud L, Skare JC, Milunsky A. Partial duplication of Xp: a case report and review of previously reported cases. Amer J Med Genet 1991: 40: 280-283) to have a de novo partial duplication of Xp. At that time, she was a 24-year-old woman with short stature, irregular menses, other abnormalities suggestive of Turner syndrome, and paranoid schizophrenia. Recently, FISH analysis demonstrated that she has an inverted duplication (X)(p22.1p11.2) and a microscopic deletion (X)(p22.2p22.3) between DXS1233 and DXS7108 spanning approximately 16-18 cM. Patient 2 is a 14-year-old girl with short stature, learning disabilities, and paranoid schizophrenia. High-resolution chromosome analysis revealed a de novo deletion involving Xp22. FISH analysis showed that the deletion (X)(p22.2p22.3) spanned 10-12 cM between AFMB290XG5 and DXS1060. Given that deletions of Xp22 are not common events, the occurrence of two unrelated schizophrenia patients with an overlapping deletion of this region would be extraordinarily rare. Hence, the deletion within Xp22.3 almost certainly contains a gene involved in the pathogenesis of paranoid schizophrenia.

  4. High-density physical mapping of a 3-Mb region in Xp22.3 and refined localization of the gene for X-linked recessive chondrodysplasia punctata (CDPX1)

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    Wang, I.; Levilliers, J.; Petit, C. [Institut Pasteur, Paris (France)] [and others

    1995-03-20

    The study of patients with chromosomal rearrangements has led to the mapping of the gene responsible for X-linked recessive chondrodysplasia punctata (CDPX1; MIM 302950) to the distal part of the Xp22.3 region, between the loci PABX and DXS31. To refine this mapping, a yeast artificial chromosome (YAC) contig map spanning this region has been constructed. Together with the YAC contig of the pseudo-autosomal region that we previously established, this map covers the terminal 6 Mb of Xp, with an average density of 1 probe every 100 kb. Newly isolated probes that detect segmental X-Y homologies on Yp and Yq suggest multiple complex rearrangements of the ancestral pseudoautosomal region during evolution. Compilation of the data obtained from the study of individuals carrying various Xp22.3 deletions led us to conclude that the CDPX disease displays incomplete penetrance and, consequently, to refine the localization of CDPX1 to a 600-kb interval immediately adjacent to the pseudoautosomal boundary. This interval, in which 12 probes are ordered, provides the starting point for the isolation of CDPX1. 67 refs., 3 figs., 2 tabs.

  5. Identifying candidate genes for X-linked hypophosphatemic rickets (HYP) in the critical region X(p22.1-p22.2)

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    Holm, L.A.; Freedner, N.L.; Maizoub, J.A. [Harvard Medical School, Boston, MA (United States)] [and others

    1994-09-01

    X-linked hypophosphatemic rickets (HYP) is the most common inherited form of rickets, characterized by a proximal renal tubular phosphate leak leading to phosphate-wasting and abnormal 1.25-dihydroxyvitamin D metabolism. The primary defect is unknown, and the candidate gene approach has thus far been unsuccessful in identifying the gene. The HYP locus has been mapped to X(p22.1-p22.2) and more recently to a 500,000 base pair region spanned by two YACs, E01138 and A0472. In an effort to identify the HYP gene in the 500 kb region, we are taking the direct selection approach. Since the tissue expressing the HYP gene is unknown, we are using cDNA libraries from a number of tissues for direct selection, including kidney, liver, thyroid, brain, spinal cord, total fetus, bone, and an osteosarcoma cell line. The tissue cDNA is hybridized to the YACs A0472 and EO1138 (obtained courtesy of Fiona Francis, Imperial Cancer Research Fund, London) in the presence of quenchers, which block repeated and ribosomal sequences on the YACs. A selected library is created from the tissues cDNAs that hybridize to the YACs. The selected cDNA library is first screened to eliminate inserts containing repeated and ribosomal sequences. The presence of the inserts on the YAC and on X(p22.1-p22.2) is then verified using mapping panels. Candidate cDNAs that make it through this analysis are sequenced. Our first attempts at making selected libraries resulted in a number of contaminants. Three separate libraries are currently under construction, using the following combinations of tissue cDNA libraries: (1) kidney, liver, and thyroid; (2) brain, spinal cord, and total fetus; and (3) bone and an osteosarcoma cell line. We will discuss transcripts obtained from these libraries.

  6. Location interval at Xp22.3 for X-linked chondrodysplasia punctata

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    Sheffield, L.; Hutchison, W.; Holloway, A. [Murdoch Institute for Research into Birth Defects, Paris (France)] [and others

    1994-09-01

    The literature shows that there is a gene for chondropdysplasia punctata (CDP) located at Xp22.3 from the study of chromosomal rearrangements involving Xp. It is also suspected that there are genes for short stature and mental retardation nearby. Petit has described a family of brachytelephalangic CDP that was due to a submicroscopic interstitial deletion of Xp22.3. Symmetrical (mild) CDP seems to be identical to brachytelephalangic CDP clinically, has variable features of short stature and mental retardation, and has a preponderance of affected males. We describe results using DNA probes from Xp22.3 in 10 patients with radiologically proven symmetrical CDP. Other known genes in this region have a high proportion of deletions as we screened our patients for deletions in DXYS20, MIC2, PABX, DXYS159X, DXS283, DXS285, J502(PCR), DXS31, DXS43 (listed distally to proximally). No deletions were found. We have also studied a fetus with proven CDP who has a X,Y translocation (46,V,t(X;Y)(p22.3;q12)mat). This patient was deleted for all distal probes up to J502(PCR). It is not yet known where the breakpoint lies but it may be just proximal to the CDP gene. The results of the 10 symmetrical CDPs and the X;Y translocation fetus are presented with further definition of the X chromosomal breakpoint in the translocation.

  7. Xp22. 3 deletions in isolated familial Kallmann's syndrome

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    Hardelin, J.P.; Levilliers, J.; Legouis, R.; Petit, C. (Institut Pasteur, Paris (France)); Young, J.; Pholsena, M.; Schaison, G. (Centre Hospitalier de Bicetre, Le Kremlin-Bicetre (France)); Kirk, J.; Bouloux, P. (Royal Free Hospital, London (United Kingdom))

    1993-04-01

    Several familial cases of Kallmann's syndrome (KS) have been reported, among which the X-chromosome-linked mode of inheritance is the most frequent. The gene responsible for the X-linked KS has been localized to the terminal part of the X-chromosome short arm (Xp22.3 region), immediately proximal to the steroid sulfatase gene responsible for X-linked ichthyosis. Large deletions of this region have been previously shown in patients affected with both X-linked ichthyosis and KS. The authors report here the search for Xp22.3 deletions in 20 unrelated males affected with isolated X-linked KS. Only 2 deletions were found using Southern blot analysis, indicating that large deletions are uncommon in patients affected with KS alone. Both deletions were shown to include the entire KAL gene responsible for X-linked KS. The patients carrying these deletions exhibit additional clinical anomalies, which are discussed: unilateral renal aplasia, unilateral absence of vas deferens, mirror movements, and sensory neural hearing loss. 47 refs., 2 figs., 1 tab.

  8. Copy number gain at Xp22.31 includes complex duplication rearrangements and recurrent triplications.

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    Liu, Pengfei; Erez, Ayelet; Nagamani, Sandesh C Sreenath; Bi, Weimin; Carvalho, Claudia M B; Simmons, Alexandra D; Wiszniewska, Joanna; Fang, Ping; Eng, Patricia A; Cooper, M Lance; Sutton, V Reid; Roeder, Elizabeth R; Bodensteiner, John B; Delgado, Mauricio R; Prakash, Siddharth K; Belmont, John W; Stankiewicz, Pawel; Berg, Jonathan S; Shinawi, Marwan; Patel, Ankita; Cheung, Sau Wai; Lupski, James R

    2011-05-15

    Genomic instability is a feature of the human Xp22.31 region wherein deletions are associated with X-linked ichthyosis, mental retardation and attention deficit hyperactivity disorder. A putative homologous recombination hotspot motif is enriched in low copy repeats that mediate recurrent deletion at this locus. To date, few efforts have focused on copy number gain at Xp22.31. However, clinical testing revealed a high incidence of duplication of Xp22.31 in subjects ascertained and referred with neurobehavioral phenotypes. We systematically studied 61 unrelated subjects with rearrangements revealing gain in copy number, using multiple molecular assays. We detected not only the anticipated recurrent and simple nonrecurrent duplications, but also unexpectedly identified recurrent triplications and other complex rearrangements. Breakpoint analyses enabled us to surmise the mechanisms for many of these rearrangements. The clinical significance of the recurrent duplications and triplications were assessed using different approaches. We cannot find any evidence to support pathogenicity of the Xp22.31 duplication. However, our data suggest that the Xp22.31 duplication may serve as a risk factor for abnormal phenotypes. Our findings highlight the need for more robust Xp22.31 triplication detection in that such further gain may be more penetrant than the duplications. Our findings reveal the distribution of different mechanisms for genomic duplication rearrangements at a given locus, and provide insights into aspects of strand exchange events between paralogous sequences in the human genome.

  9. A Turner syndrome neurocognitive phenotype maps to Xp22.3

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    Elder Frederick F

    2007-05-01

    Full Text Available Abstract Background Turner syndrome (TS is associated with a neurocognitive phenotype that includes selective nonverbal deficits, e.g., impaired visual-spatial abilities. We previously reported evidence that this phenotype results from haploinsufficiency of one or more genes on distal Xp. This inference was based on genotype/phenotype comparisons of individual girls and women with partial Xp deletions, with the neurocognitive phenotype considered a dichotomous trait. We sought to confirm our findings in a large cohort (n = 47 of adult women with partial deletions of Xp or Xq, enriched for subjects with distal Xp deletions. Methods Subjects were recruited from North American genetics and endocrinology clinics. Phenotype assessment included measures of stature, ovarian function, and detailed neurocognitive testing. The neurocognitive phenotype was measured as a quantitative trait, the Turner Syndrome Cognitive Summary (TSCS score, derived from discriminant function analysis. Genetic analysis included karyotyping, X inactivation studies, fluorescent in situ hybridization, microsatellite marker genotyping, and array comparative genomic hybridization. Results We report statistical evidence that deletion of Xp22.3, an interval containing 31 annotated genes, is sufficient to cause the neurocognitive phenotype described by the TSCS score. Two other cardinal TS features, ovarian failure and short stature, as well as X chromosome inactivation pattern and subject's age, were unrelated to the TSCS score. Conclusion Detailed mapping suggests that haploinsufficiency of one or more genes in Xp22.3, the distal 8.3 megabases (Mb of the X chromosome, is responsible for a TS neurocognitive phenotype. This interval includes the 2.6 Mb Xp-Yp pseudoautosomal region (PAR1. Haploinsufficiency of the short stature gene SHOX in PAR1 probably does not cause this TS neurocognitive phenotype. Two genes proximal to PAR1 within the 8.3 Mb critical region, STS and NLGN4X, are

  10. X-linked ocular albinism and sensorineural deafness: Linkage to Xp22. 3

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    Winship, I.M.; Babaya, M.; Ramesar, R.S. (Univ. of Cape Town Medical School (South Africa))

    1993-11-01

    X-linked ocular albinism with late-onset sensorineural deafness (OASD) is an autonomous disorder that poses significant clinical problems, causing affected individuals to be blind and deaf by early middle age. Classical X-linked ocular albinism (without deafness; OA1) has recently been linked to markers in the Xp22.2-Xp22.3 region of the human genome. In the present report, a large South African family with OASD was investigated at the molecular level and tight linkage was found to the DXS452 locus at Xp22.3 using 25 informative meioses, with a maximum lod score of 7.1 at a recombination fraction of 0.00. These findings suggest that OA1 and OASD are allelic variants or that they may be due to contiguous gene defects. 12 refs., 1 fig.

  11. Positional Cloning in Xp22 : towards the isolation of the gene involved in X-linked retinoschisis

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    Vosse, Esther van de

    1998-01-01

    The study was aimed at the positional cloning of disease genes in Xp22.1-p22.2. To this end a YAC contig covering this region was constructed. To identify candidate genes for the diseases localised in this region exon trapping was applied. Several novel transcripts were isolated from the region, of

  12. Development and physical analysis of YAC contigs covering 7 Mb of Xp22.3-p22.2

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    Herrell, S.; Novo, F.J.; Charlton, R. [Univ. of Cambridge (United Kingdom)] [and others

    1995-01-20

    A total of YAC clones have been isolated from the region of Xp22.2-p22.3 extending from the amelogenin gene locus to DXS31. Restriction analysis of these clones in association with STS contenting and end clone analysis has facilitated the construction of 6 contigs covering a total of 7 Mb in which 20 potential CpG islands have been located. Thirty new STSs have been developed from probe and YAC end clone sequences, and these have been used in the analysis of patients suffering from different combinations of chondrodysplasia punctata, mental retardation, X-linked ichthyosis, and Kallmann syndrome. The results suggest that (1) the gene for chondrodysplasia punctata must lie between the X chromosome pseudoautosomal boundary (PABX) and DXS1145; (2) a gene for mental retardation lies between DXS1145 and the sequence tagged site GS1; and (3) the gene for ocular albinism type 1 lies proximal to the STS G13. The CpG islands within the YAC contigs constitute valuable markers for the potential positions of genes. Genes found associated with any of these potential CpG islands would be possible candidates for the disease genes mentioned above. 47 refs., 3 figs., 5 tabs.

  13. X-linked dominant cone-rod degeneration: Linkage mapping of a new locus for retinitis pigmentosa (RP15) to Xp22.13-p22.11

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    McGuire, R.E.; Sullivan, L.S.; Daiger, S.P. [Univ. of Texas-Houston Health Science Center, TX (United States)] [and others

    1995-07-01

    Retinitis pigmentosa is the name given to a heterogeneous group of hereditary retinal degenerations characterized by progressive visual field loss, pigmentary changes of the retina, abnormal electroretinograms, and, frequently, night blindness. In this study, we investigated a family with dominant cone-rod degeneration, a variant form of retinitis pigmentosa. We used microsatellite markers to test for linkage to the disease locus and exluded all mapped autosomal loci. However, a marker from the short arm of the X chromosome, DXS989, showed 0% recombination to the disease locus, with a maximum lod (log-odds) score of 3.3. On the basis of this marker, the odds favoring X-linked dominant versus autosomal dominant inheritance are > 10{sup 5}:1. Haplotype analysis using an additional nine microsatellite markers places the disease locus in the Xp22.13-p22.11 region and excludes other X-linked disease loci causing retinal degeneration. The clinical expression of the retinal degeneration is consistent with X-linked dominant inheritance with milder, variable effects of Lyonization affecting expression in females. On the basis of these data we propose that this family has a novel form of dominant, X-linked cone-rod degeneration with the gene symbol {open_quotes}RP15{close_quotes}. 17 refs., 2 figs., 4 tabs.

  14. X-linked mental retardation, short stature, microcephaly and hypogonadism maps to Xp22.1-p21.3 in a Belgian family.

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    Van Esch, Hilde; Zanni, Ginevra; Holvoet, Maureen; Borghgraef, Martine; Chelly, Jamel; Fryns, Jean-Pierre; Devriendt, Koenraad

    2005-01-01

    X-linked mental retardation (XLMR) is a heterogeneous disorder that can be classified as either non-specific (MRX), when mental retardation is the only feature, or as syndromic mental retardation (MRXS). Genetic defects underlying XLMR are being identified at a rapid pace, often starting from X-chromosomal aberrations and XLMR families with a well-defined linkage interval. Here, we present a new family with a syndromic form of XLMR, including mild mental retardation, short stature, microcephaly and hypogonadism. Two-point linkage analysis with 24 polymorphic markers spanning the entire X chromosome was carried out. We could assign the causative gene to a 6 cM interval in Xp22.1-p21.3, with a maximum LOD score of 2.61 for markers DXS989 and DXS1061 at theta = 0.00. No mutations were found in the presented family for two known MRX genes mapping to this interval, ARX and IL1RAPL-1. These data indicate that the interval Xp22.1-p21.3 contains at least one additional MRXS gene.

  15. Congenital nasal pyriform aperture stenosis and ocular albinism co-occurring in a sibship with a maternally-inherited 97 kb Xp22.2 microdeletion.

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    Somsen, David; Davis-Keppen, Laura; Crotwell, Patricia; Flanagan, Jason; Munson, Patrick; Stein, Quinn

    2014-05-01

    Congenital Nasal Pyriform Aperture Stenosis (CNPAS) is a rare congenital malformation caused by overgrowth of the maxillary bone. We report on two patients, brothers born 3 and 1½ years apart, both presented at birth with radiographically diagnosed CNPAS. Both siblings also were born with ocular albinism, which is known to have X-linked inheritance. Subsequent genetic testing demonstrated a 97 kb deletion in the p arm of the X chromosome in both siblings and their mother. This deletion encompasses a gene known to cause ocular albinism (GPR143), as well as partial deletion of two other genes, TBL1X and SHROOM2. This is the first reported case of CNPAS in siblings, both males, sharing a maternally inherited Xp22.2 deletion.

  16. The sequence organization of Yp/proximal Xq homologous regions of the human sex chromosomes is highly conserved.

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    Sargent, C A; Briggs, H; Chalmers, I J; Lambson, B; Walker, E; Affara, N A

    1996-03-01

    Detailed deletion analysis of patients with breakpoints in Yp has allowed the definition of two distinct intervals on the Y chromosome short arm outside the pseudoautosomal region that are homologous to Xq2l.3. Detailed YAC contigs have been developed over these regions on both the X and Y chromosomes, and the relative order of markers has been compared to assess whether rearrangements on either sex chromosome have occurred since the transposition events creating these patterns of homology. On the X chromosome, the region forms almost one contiguous block of homology, whereas on the Y chromosome, there has been one major rearrangement leading to the two separate Yp-Xq2l blocks of homology. The rearrangement breakpoint has been mapped. Within these separate X-Y homologous blocks on Yp, the order of loci homologous to X has been conserved to a high degree between the sex chromosomes. With the exception of the amelogenin gene (proximal Yp block), all the XY homologous sequences in the two Yp blocks have homolognes in Xq2l.3, with the former having its X counterpart in Xp22.2. This suggests an independent evolutionary event leading to the formation of the amelogenin X-Y homology.

  17. Syndromic form of X-linked mental retardation with marked hypotonia in early life, severe mental handicap, and difficult adult behavior maps to Xp22.

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    Turner, Gillian; Gedeon, Agi; Kerr, Bronwyn; Bennett, Rachael; Mulley, John; Partington, Michael

    2003-03-15

    An X-linked recessive syndromic form of mental retardation is described in a family in which 10 males in four generations were affected. The main manifestations were severe to profound intellectual disability, muscular hypotonia in childhood, delayed walking, and difficult, aggressive behavior. There was a moderate reduction both in occipitofrontal circumference (OFC) and height and a similar facial appearance, triangular in shape with a high forehead, prominent ears, and a small pointed chin. Linkage analysis located the gene at Xp22 with maximum lod scores of 4.8 at theta = 0.0 for markers mapping between the closest recombination points at DXS7104 and DXS418. The physical length of this region is approximately 6 Mb. Mutations in the GRPR gene and M6b genes were excluded by sequence analysis. Nearby genes in which mutations are known to be associated with mental retardation (RPS6KA3, STK9, and VCXA, B and C), were excluded by position.

  18. Chromosomal instability in Streptomyces avermitilis: major deletion in the central region and stable circularized chromosome

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    Wen Ying

    2010-07-01

    Full Text Available Abstract Background The chromosome of Streptomyces has been shown to be unstable, frequently undergoing gross chromosomal rearrangements. However, the mechanisms underlying this phenomenon remain unclear, with previous studies focused on two chromosomal ends as targets for rearrangements. Here we investigated chromosomal instability of Streptomyces avermitilis, an important producer of avermectins, and characterized four gross chromosomal rearrangement events, including a major deletion in the central region. The present findings provide a valuable contribution to the mechanistic study of genetic instability in Streptomyces. Results Thirty randomly-selected "bald" mutants derived from the wild-type strain all contained gross chromosomal rearrangements of various types. One of the bald mutants, SA1-8, had the same linear chromosomal structure as the high avermectin-producing mutant 76-9. Chromosomes of both strains displayed at least three independent chromosomal rearrangements, including chromosomal arm replacement to form new 88-kb terminal inverted repeats (TIRs, and two major deletions. One of the deletions eliminated the 36-kb central region of the chromosome, but surprisingly did not affect viability of the cells. The other deletion (74-kb was internal to the right chromosomal arm. The chromosome of another bald mutant, SA1-6, was circularized with deletions at both ends. No obvious homology was found in all fusion sequences. Generational stability analysis showed that the chromosomal structure of SA1-8 and SA1-6 was stable. Conclusions Various chromosomal rearrangements, including chromosomal arm replacement, interstitial deletions and chromosomal circularization, occurred in S. avermitilis by non-homologous recombination. The finding of an inner deletion involving in the central region of S. avermitilis chromosome suggests that the entire Streptomyces chromosome may be the target for rearrangements, which are not limited, as previously

  19. Contiguous gene syndromes due to deletions in the distal short arm of the human X chromosome

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    Ballabio, A.; Andria, G. (Univ. of Reggio Calabria, Catanzaro (Italy)); Bardoni, B.; Fraccaro, M.; Maraschio, P.; Zuffardi, O.; Guioli, S.; Camerino, G. (Univ. of Pavia (Italy)); Carrozzo, R. (Univ. of Naples (Italy)); Bick, D.; Campbell, L. (Univ. of Texas, San Antonio (USA)); Hamel, B. (Univ. of Nijmegen (Netherlands)); Ferguson-Smith, M.A. (Univ. of Cambridge (England)); Gimelli, G. (G. Gaslini Institute, Genoa (Italy))

    1989-12-01

    Mendelian inherited disorders to deletions of adjacent genes on a chromosome have been described as contiguous gene syndromes. Short stature, chondrodysplasia punctata, mental retardation, steroid sulfatase deficiency, and Kallmann syndrome have been found as isolated entities or associated in various combination in 27 patients with interstitial and terminal deletions involving the distal short are of the X chromosome. The use of cDNA and genomic probes from the Xp22-pter region allowed us to identify 12 different deletion intervals and to confirm, and further refine, the chromosomal assignment of X-linked recessive chondrodysplasia punctata and Kallmann syndrome genes. A putative pseudoautosomal gene affecting height and an X-linked nonspecific mental retardation gene have been tentatively assigned to specific intervals. The deletion panel described is a useful tool for mapping new sequences and orienting chromosome walks in the region.

  20. Encephalopathy and bilateral cataract in a boy with an interstitial deletion of Xp22 comprising the CDKL5 and NHS genes.

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    Van Esch, Hilde; Jansen, Anna; Bauters, Marijke; Froyen, Guy; Fryns, Jean-Pierre

    2007-02-15

    We describe a male patient with a deletion at Xp22, detected by high resolution X-array CGH. The clinical phenotype present in this infant boy, consists of severe encephalopathy, congenital cataracts and tetralogy of Fallot and can be attributed to the deletion of the genes within the interval. Among these deleted genes are the gene for Nance-Horan syndrome and the cyclin-dependent kinase-like 5 gene (CDKL5), responsible for the early seizure variant of Rett syndrome. This is the first description of a male patient with a deletion of these genes, showing the involvement of CDKL5 in severe epileptic encephalopathy in males. Moreover it illustrates the added value of high resolution array-CGH in molecular diagnosis of mental retardation-multiple congenital anomaly cases.

  1. Hypermethylated Chromosome Regions in Nine Fish Species with Heteromorphic Sex Chromosomes.

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    Schmid, Michael; Steinlein, Claus; Yano, Cassia F; Cioffi, Marcelo B

    2015-01-01

    Sites and amounts of 5-methylcytosine (5-MeC)-rich chromosome regions were detected in the karyotypes of 9 Brazilian species of Characiformes fishes by indirect immunofluorescence using a monoclonal anti-5-MeC antibody. These species, belonging to the genera Leporinus, Triportheus and Hoplias, are characterized by highly differentiated and heteromorphic ZW and XY sex chromosomes. In all species, the hypermethylated regions are confined to constitutive heterochromatin. The number and chromosome locations of hypermethylated heterochromatic regions in the karyotypes are constant and species-specific. Generally, heterochromatic regions that are darkly stained by the C-banding technique are distinctly hypermethylated, but several of the brightly fluorescing hypermethylated regions merely exhibit moderate or faint C-banding. The ZW and XY sex chromosomes of all 9 analyzed species also show species-specific heterochromatin hypermethylation patterns. The analysis of 5-MeC-rich chromosome regions contributes valuable data for comparative cytogenetics of closely related species and highlights the dynamic process of differentiation operating in the repetitive DNA fraction of sex chromosomes.

  2. A Syntenic Region Conserved from Fish to Mammalian X Chromosome

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    Guijun Guan

    2014-01-01

    Full Text Available Sex chromosomes bearing the sex-determining gene initiate development along the male or female pathway, no matter which sex is determined by XY male or ZW female heterogamety. Sex chromosomes originate from ancient autosomes but evolved rapidly after the acquisition of sex-determining factors which are highly divergent between species. In the heterogametic male system (XY system, the X chromosome is relatively evolutionary silent and maintains most of its ancestral genes, in contrast to its Y counterpart that has evolved rapidly and degenerated. Sex in a teleost fish, the Nile tilapia (Oreochromis niloticus, is determined genetically via an XY system, in which an unpaired region is present in the largest chromosome pair. We defined the differences in DNA contents present in this chromosome with a two-color comparative genomic hybridization (CGH and the random amplified polymorphic DNA (RAPD approach in XY males. We further identified a syntenic segment within this region that is well conserved in several teleosts. Through comparative genome analysis, this syntenic segment was also shown to be present in mammalian X chromosomes, suggesting a common ancestral origin of vertebrate sex chromosomes.

  3. A child with mild X-linked intellectual disability and a microduplication at Xp22.12 including RPS6KA3.

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    Tejada, María-Isabel; Martínez-Bouzas, Cristina; García-Ribes, Ainhoa; Larrucea, Susana; Acquadro, Francesco; Cigudosa, Juan-C; Belet, Stefanie; Froyen, Guy; López-Aríztegui, Maria-Asun

    2011-10-01

    Multiplex ligation-dependent probe amplification (MLPA) and array- comparative genomic hybridization analysis have been proven to be useful in the identification of submicroscopic copy-number imbalances in families with nonsyndromic X-linked intellectual disability (NS-XLID). Here we report the first description of a child with mild intellectual disability and a submicroscopic duplication at Xp22.12 identified by MLPA with a P106 MRX kit (MRC-Holland, Amsterdam, Netherlands) and further confirmed and characterized with a custom 244-k oligo-array, fluorescence in situ hybridization, quantitative polymerase chain reaction (qPCR), and immunoblotting. This 1.05-megabase duplication encompasses 7 genes, RPS6KA3 being the only of these genes known to be related to ID. The proband was an 8-year-old boy referred to the genetics unit for psychomotor retardation and learning disabilities. Both maternal brothers also showed learning difficulties and delayed language during childhood in a similar way to the proband. These boys also carried the duplication, as did the healthy mother and grandmother of the proband. The same duplication was also observed in the 5-year-old younger brother who presented with features of developmental delay and learning disabilities during the previous year. Increased RPS6KA3/RSK2 levels were demonstrated in the proband by qPCR and immunoblotting. To our knowledge, this is the first family identified with a submicroscopic duplication including the entire RPS6KA3/RSK2 gene, and our findings suggest that an increased dose of this gene is responsible for a mild form of NS-XLID.

  4. ORDERING OF MARKERS IN THE PERICENTROMERIC REGION OF CHROMOSOME-10

    NARCIS (Netherlands)

    HOFSTRA, RMW; STELWAGEN, T; PASINI, B; VANDERVEEN, AY; PONDER, BAJ; NAKAMURA, Y; ROMEO, G; BUYS, CHCM

    Seven polymorphic cosmids previously assigned to 10cen-q11.2 were mapped between D10S34 and RBP3, and ordered by interphase in situ hybridization and yeast artificial chromosome analysis. Some of the presumed unique sequences from the centromeric region have homologies either within the same region

  5. [Fluorescence in situ hybridization with DNA probes derived from individual chromosomes and chromosome regions].

    Science.gov (United States)

    Bogomolov, A G; Karamysheva, T V; Rubtsov, N B

    2014-01-01

    A significant part of the eukaryotic genomes consists of repetitive DNA, which can form large clusters or distributed along euchromatic chromosome regions. Repeats located in chromosomal regions make a problem in analysis and identification of the chromosomal material with fluorescence in situ hybridization (FISH). In most cases, the identification of chromosome regions using FISH requires detection of the signal produced with unique sequences. The feasibility, advantages and disadvantages of traditional methods of suppression of repetitive DNA hybridization, methods of repeats-free probe construction and methods of chromosome-specific DNA sequences visualization using image processing of multicolor FISH results are considered in the paper. The efficiency of different techniques for DNA probe generation, different FISH protocols, and image processing of obtained microscopic images depends on the genomic size and structure of analyzing species. This problem was discussed and different approaches were considered for the analysis of the species with very large genome, rare species and species which specimens are too small in size to obtain the amount of genomic and Cot-1 DNA required for suppression of repetitive DNA hybridization.

  6. Rapid generation of region-specific probes by chromosome microdissection: Application to the identification of chromosomal rearrangements

    Energy Technology Data Exchange (ETDEWEB)

    Trent, J.M.; Guan, X.Y.; Zang, J.; Meltzer, P.S. (Univ. of Michigan, Ann Arbor (United States))

    1993-01-01

    The authors present results using a novel strategy for chromosome microdissection and direct in vitro amplification of specific chromosomal regions, to identify cryptic chromosome alterations, and to rapidly generate region-specific genomic probes. First, banded chromosomes are microdissected and directly PCR amplified by a procedure which eliminates microchemistry (Meltzer, et al., Nature Genetics, 1:24, 1992). The resulting PCR product can be used for several applications including direct labeling for fluorescent in situ hybridization (FISH) to normal metaphase chromosomes. A second application of this procedure is the extremely rapid generation of chromosome region-specific probes. This approach has been successfully used to determine the derivation of chromosome segments unidentifiable by standard chromosome banding analysis. In selected instances these probes have also been used on interphase nuclei and provides the potential for assessing chromosome abnormalities in a variety of cell lineages. The microdissection probes (which can be generated in <24 hours) have also been utilized in direct library screening and provide the possibility of acquiring a significant number of region-specific probes for any chromosome band. This procedure extends the limits of conventional cytogenetic analysis by providing an extremely rapid source of numerous band-specific probes, and by enabling the direct analysis of essentially any unknown chromosome region.

  7. Delineation and analysis of chromosomal regions specifying Yersinia pestis.

    Science.gov (United States)

    Derbise, Anne; Chenal-Francisque, Viviane; Huon, Christèle; Fayolle, Corinne; Demeure, Christian E; Chane-Woon-Ming, Béatrice; Médigue, Claudine; Hinnebusch, B Joseph; Carniel, Elisabeth

    2010-09-01

    Yersinia pestis, the causative agent of plague, has recently diverged from the less virulent enteropathogen Yersinia pseudotuberculosis. Its emergence has been characterized by massive genetic loss and inactivation and limited gene acquisition. The acquired genes include two plasmids, a filamentous phage, and a few chromosomal loci. The aim of this study was to characterize the chromosomal regions acquired by Y. pestis. Following in silico comparative analysis and PCR screening of 98 strains of Y. pseudotuberculosis and Y. pestis, we found that eight chromosomal loci (six regions [R1pe to R6pe] and two coding sequences [CDS1pe and CDS2pe]) specified Y. pestis. Signatures of integration by site specific or homologous recombination were identified for most of them. These acquisitions and the loss of ancestral DNA sequences were concentrated in a chromosomal region opposite to the origin of replication. The specific regions were acquired very early during Y. pestis evolution and were retained during its microevolution, suggesting that they might bring some selective advantages. Only one region (R3pe), predicted to carry a lambdoid prophage, is most likely no longer functional because of mutations. With the exception of R1pe and R2pe, which have the potential to encode a restriction/modification and a sugar transport system, respectively, no functions could be predicted for the other Y. pestis-specific loci. To determine the role of the eight chromosomal loci in the physiology and pathogenicity of the plague bacillus, each of them was individually deleted from the bacterial chromosome. None of the deletants exhibited defects during growth in vitro. Using the Xenopsylla cheopis flea model, all deletants retained the capacity to produce a stable and persistent infection and to block fleas. Similarly, none of the deletants caused any acute flea toxicity. In the mouse model of infection, all deletants were fully virulent upon subcutaneous or aerosol infections. Therefore

  8. Delineation and Analysis of Chromosomal Regions Specifying Yersinia pestis▿ †

    Science.gov (United States)

    Derbise, Anne; Chenal-Francisque, Viviane; Huon, Christèle; Fayolle, Corinne; Demeure, Christian E.; Chane-Woon-Ming, Béatrice; Médigue, Claudine; Hinnebusch, B. Joseph; Carniel, Elisabeth

    2010-01-01

    Yersinia pestis, the causative agent of plague, has recently diverged from the less virulent enteropathogen Yersinia pseudotuberculosis. Its emergence has been characterized by massive genetic loss and inactivation and limited gene acquisition. The acquired genes include two plasmids, a filamentous phage, and a few chromosomal loci. The aim of this study was to characterize the chromosomal regions acquired by Y. pestis. Following in silico comparative analysis and PCR screening of 98 strains of Y. pseudotuberculosis and Y. pestis, we found that eight chromosomal loci (six regions [R1pe to R6pe] and two coding sequences [CDS1pe and CDS2pe]) specified Y. pestis. Signatures of integration by site specific or homologous recombination were identified for most of them. These acquisitions and the loss of ancestral DNA sequences were concentrated in a chromosomal region opposite to the origin of replication. The specific regions were acquired very early during Y. pestis evolution and were retained during its microevolution, suggesting that they might bring some selective advantages. Only one region (R3pe), predicted to carry a lambdoid prophage, is most likely no longer functional because of mutations. With the exception of R1pe and R2pe, which have the potential to encode a restriction/modification and a sugar transport system, respectively, no functions could be predicted for the other Y. pestis-specific loci. To determine the role of the eight chromosomal loci in the physiology and pathogenicity of the plague bacillus, each of them was individually deleted from the bacterial chromosome. None of the deletants exhibited defects during growth in vitro. Using the Xenopsylla cheopis flea model, all deletants retained the capacity to produce a stable and persistent infection and to block fleas. Similarly, none of the deletants caused any acute flea toxicity. In the mouse model of infection, all deletants were fully virulent upon subcutaneous or aerosol infections. Therefore

  9. Major factors influencing linkage disequilibrium by analysis of different chromosome regions in distinct populations: demography, chromosome recombination frequency and selection.

    Science.gov (United States)

    Zavattari, P; Deidda, E; Whalen, M; Lampis, R; Mulargia, A; Loddo, M; Eaves, I; Mastio, G; Todd, J A; Cucca, F

    2000-12-12

    Linkage disequilibrium (LD) mapping of disease genes is complicated by population- and chromosome-region-specific factors. We have analysed demographic factors by contrasting intermarker LD results obtained in a large cosmopolitan population (UK), a large genetic isolate (Sardinia) and a subisolate (village of Gavoi) for two regions of the X chromosome. A dramatic increase of LD was found in the subisolate. Demographic history of populations therefore influences LD. Chromosome-region-specific effects, namely the pattern and frequency of homologous recombination, were next delineated by the analysis of chromosome 6p21, including the HLA region. Patterns of global LD in this region were very similar in the UK and Sardinian populations despite their entirely distinct demographies, and correlate well with the pattern of recombinations. Nevertheless, haplotypes extend across recombination hot spots indicative of selection of certain haplotypes. Subisolate aside, chromosome-region-specific differences in LD patterns appear to be more important than the differences in intermarker LD between distinct populations.

  10. Organization of the R chromosome region in maize. Triennial report

    Energy Technology Data Exchange (ETDEWEB)

    Kermicle, J.L.

    1979-12-01

    Anthocyanin pigmentation in maize is strain and tissue specific. The primary source of variation is represented in maize races indigenous to widely separated geographic regions of North and South America. Secondary sources include variants which have appeared spontaneously in culture, arose following mutagenic treatment, or were incited through paramutation or by means of controlling elements. Much of the observed variation is attributable to a narrowly restricted segment of chromosome 10, designated the R region. The studies on R organization seek to analyze this variation in terms of the number, kind and arrangement of the components involved.

  11. Regions of XY homology in the pig X chromosome and the boundary of the pseudoautosomal region

    Directory of Open Access Journals (Sweden)

    Skinner Benjamin M

    2013-01-01

    Full Text Available Abstract Background Sex chromosomes are subject to evolutionary pressures distinct from the remainder of the genome, shaping their structure and sequence content. We are interested in the sex chromosomes of domestic pigs (Sus scrofa, how their structure and gene content compares and contrasts with other mammalian species, and the role of sex-linked genes in fertility. This requires an understanding of the XY-homologous sequence on these chromosomes. To this end, we performed microarray-based comparative genomic hybridisation (array-CGH with male and female Duroc genomic DNA on a pig X-chromosome BAC tiling-path microarray. Putative XY-homologous BACs from regions of interest were subsequently FISH mapped. Results We show that the porcine PAR is approximately 6.5-6.9 Mb at the beginning of the short arm of the X, with gene content reflective of the artiodactyl common ancestor. Our array-CGH data also shows an XY-homologous region close to the end of the X long arm, spanning three X BACs. These BACs were FISH mapped, and paint the entire long arm of SSCY. Further clones of interest revealed X-autosomal homology or regions containing repetitive content. Conclusions This study has identified regions of XY homology in the pig genome, and defined the boundary of the PAR on the X chromosome. This adds to our understanding of the evolution of the sex chromosomes in different mammalian lineages, and will prove valuable for future comparative genomic work in suids and for the construction and annotation of the genome sequence for the sex chromosomes. Our finding that the SSCYq repetitive content has corresponding sequence on the X chromosome gives further insight into structure of SSCY, and suggests further functionally important sequences remain to be discovered on the X and Y.

  12. Isolation and characterization of a steroid sulfatase cDNA clone: genomic deletions in patients with X-chromosome-linked ichthyosis

    Energy Technology Data Exchange (ETDEWEB)

    Ballabio, A.; Parenti, G.; Carrozzo, R.; Sebastio, G.; Andria, G.; Buckle, V.; Fraser, N.; Craig, I.; Rocchi, M.; Romeo, G.; Jobsis, A.C.; Persico, M.G.

    1987-07-01

    The authors have isolated several cDNA clones from a lambdagt11 expression library by screening with antibodies prepared against the microsomal enzyme steroid sulfatase, which is deficient in classical X-chromosome-linked ichthyosis patients. One of these clones (p422) has been assigned by mapping with a somatic cell hybrid panel and by in situ hybridization to Xp22.3. Clone p422 therefore has a coincident localization with the previously identified locus for steroid sulfatase expression in the region of the X chromosome escaping from inactivation. Twelve steroid sulfatase-deficient patients, including eight cases of classical ichthyosis, were found to be deleted for genomic sequences detected by the clone.

  13. [Chromosomal variation in Chironomus plumosus L. (Diptera, Chironomidae) from populations of Bryansk region, Saratov region (Russia), and Gomel region (Belarus)].

    Science.gov (United States)

    Belyanina, S I

    2015-02-01

    Cytogenetic analysis was performed on samples of Chironomus plumosus L. (Diptera, Chironomidae) taken from waterbodies of various types in Bryansk region (Russia) and Gomel region (Belarus). Karyotypes of specimens taken from stream pools of the Volga were used as reference samples. The populations of Bryansk and Gomel regions (except for a population of Lake Strativa in Starodubskii district, Bryansk region) exhibit broad structural variation, including somatic mosaicism for morphotypes of the salivary gland chromosome set, decondensation of telomeric sites, and the presence of small structural changes, as opposed to populations of Saratov region. As compared with Saratov and Bryansk regions, the Balbiani ring in the B-arm of chromosome I is repressed in populations of Gomel region. It is concluded that the chromosome set of Ch. plumosus in a range of waterbodies of Bryansk and Gomel regions is unstable.

  14. Chromosome region-specific libraries for human genome analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kao, Fa-Ten.

    1991-01-01

    We have made important progress since the beginning of the current grant year. We have further developed the microdissection and PCR- assisted microcloning techniques using the linker-adaptor method. We have critically evaluated the microdissection libraries constructed by this microtechnology and proved that they are of high quality. We further demonstrated that these microdissection clones are useful in identifying corresponding YAC clones for a thousand-fold expansion of the genomic coverage and for contig construction. We are also improving the technique of cloning the dissected fragments in test tube by the TDT method. We are applying both of these PCR cloning technique to human chromosomes 2 and 5 to construct region-specific libraries for physical mapping purposes of LLNL and LANL. Finally, we are exploring efficient procedures to use unique sequence microclones to isolate cDNA clones from defined chromosomal regions as valuable resources for identifying expressed gene sequences in the human genome. We believe that we are making important progress under the auspices of this DOE human genome program grant and we will continue to make significant contributions in the coming year. 4 refs., 4 figs.

  15. Chromosome

    Science.gov (United States)

    Chromosomes are structures found in the center (nucleus) of cells that carry long pieces of DNA. DNA ... is the building block of the human body. Chromosomes also contain proteins that help DNA exist in ...

  16. The subtelomeric region is important for chromosome recognition and pairing during meiosis

    Science.gov (United States)

    Calderón, María del Carmen; Rey, María-Dolores; Cabrera, Adoración; Prieto, Pilar

    2014-01-01

    The process of meiosis results in the formation of haploid daughter cells, each of which inherit a half of the diploid parental cells' genetic material. The ordered association of homologues (identical chromosomes) is a critical prerequisite for a successful outcome of meiosis. Homologue recognition and pairing are initiated at the chromosome ends, which comprise the telomere dominated by generic repetitive sequences, and the adjacent subtelomeric region, which harbours chromosome-specific sequences. In many organisms telomeres are responsible for bringing the ends of the chromosomes close together during early meiosis, but little is known regarding the role of the subtelomeric region sequence during meiosis. Here, the observation of homologue pairing between a pair of Hordeum chilense chromosomes lacking the subtelomeric region on one chromosome arm indicates that the subtelomeric region is important for the process of homologous chromosome recognition and pairing. PMID:25270583

  17. Analysis of the terminus region of the Caulobacter crescentus chromosome and identification of the dif site

    DEFF Research Database (Denmark)

    Jensen, Rasmus Bugge

    2006-01-01

    The terminus region of the Caulobacter crescentus chromosome and the dif chromosome dimer resolution site were characterized. The Caulobacter genome contains skewed sequences that abruptly switch strands at dif and may have roles in chromosome maintenance and segregation. Absence of dif or the Xer...

  18. Crossover Interference on Nucleolus Organizing Region-Bearing Chromosomes in Arabidopsis

    Science.gov (United States)

    Lam, Sandy Y.; Horn, Sarah R.; Radford, Sarah J.; Housworth, Elizabeth A.; Stahl, Franklin W.; Copenhaver, Gregory P.

    2005-01-01

    In most eukaryotes, crossovers are not independently distributed along the length of a chromosome. Instead, they appear to avoid close proximity to one another—a phenomenon known as crossover interference. Previously, for three of the five Arabidopsis chromosomes, we measured the strength of interference and suggested a model wherein some crossovers experience interference while others do not. Here we show, using the same model, that the fraction of interference-insensitive crossovers is significantly smaller on the remaining two chromosomes. Since these two chromosomes bear the Arabidopsis NOR domains, the possibility that these chromosomal regions influence interference is discussed. PMID:15802520

  19. Construction of a consistent YAC contig for human chromosome region 3p14.1

    NARCIS (Netherlands)

    Bardenheuer, W; Michaelis, S; Lux, A; Vieten, L; Brocker, F; Julicher, K; Willers, C; Siebert, R; Smith, DI; vanderHout, AH; Buys, C; Schutte, J; Opalka, B

    1996-01-01

    Chromosomal deletions and translocations of human chromosome region 3p14 are observed in various human malignancies and suggest the existence of a tumor suppressor gene locus within this region. Tumors most frequently affected by these aberrations are small-cell lung cancer and renal-cell carcinoma.

  20. Topological Organization of Multi-chromosomal Regions by Firre

    Science.gov (United States)

    Hacisuleyman, Ezgi; Goff, Loyal A.; Trapnell, Cole; Williams, Adam; Henao-Mejia, Jorge; Sun, Lei; McClanahan, Patrick; Hendrickson, David G.; Sauvageau, Martin; Kelley, David R.; Morse, Michael; Engreitz, Jesse; Lander, Eric S.; Guttman, Mitch; Lodish, Harvey F.; Flavell, Richard; Raj, Arjun; Rinn, John L.

    2014-01-01

    RNA is known to be an abundant and important structural component of the nuclear matrix, including long noncoding RNAs (lncRNA). Yet the molecular identities, functional roles, and localization dynamics of lncRNAs that influence nuclear architecture remain poorly understood. Here, we describe one lncRNA, Firre, that interacts with the nuclear matrix factor hnRNPU, through a 156 bp repeating sequence and Firre localizes across a ~5 Mb domain on the X-chromosome. We further observed Firre localization across at least five distinct trans-chromosomal loci, which reside in spatial proximity to the Firre genomic locus on the X-chromosome. Both genetic deletion of the Firre locus or knockdown of hnRNPU resulted in loss of co-localization of these trans-chromosomal interacting loci. Thus, our data suggest a model in which lncRNAs such as Firre can interface with and modulate nuclear architecture across chromosomes. PMID:24463464

  1. Strong selective sweeps associated with ampliconic regions in great ape X chromosomes

    DEFF Research Database (Denmark)

    Nam, Kiwoong; Munch, Kasper; Hobolth, Asger

    2014-01-01

    The unique inheritance pattern of X chromosomes makes them preferential targets of adaptive evolution. We here investigate natural selection on the X chromosome in all species of great apes. We find that diversity is more strongly reduced around genes on the X compared with autosomes......, and that a higher proportion of substitutions results from positive selection. Strikingly, the X exhibits several megabase long regions where diversity is reduced more than five fold. These regions overlap significantly among species, and have a higher singleton proportion, population differentiation...... with ampliconic sequences we propose that intra-genomic conflict between the X and the Y chromosomes is a major driver of X chromosome evolution....

  2. A high-resolution interval map of the q21 region of the human X chromosome

    Energy Technology Data Exchange (ETDEWEB)

    Philippe, C.; Monaco, A.P. [ICRF Laboratories, Oxford (United Kingdom)] [and others; Arnould, C. [Laboratoire de Genetique Humaine, Vandoeuvre-les-Nancy (France)] [and others

    1995-06-10

    In a previous study, we have developed a panel of chromosomal rearrangements for the physical mapping of the q13-q21 region of the human X chromosome. Here, we report the physical localization of 36 additional polymorphic markers by polymerase chain reaction analysis. The high density of chromosomal breakpoints in Xq21 allows us to map 58 DNA loci in 22 intervals. As a result, this segment of the X chromosome is saturated with approximately three sequence tagged sites per megabase of DNA, which will facilitate the construction of a YAC contig of this region. 26 refs., 1 fig., 1 tab.

  3. Gene expression meta-analysis identifies chromosomal regions involved in ovarian cancer survival

    DEFF Research Database (Denmark)

    Thomassen, Mads; Jochumsen, Kirsten M; Mogensen, Ole;

    2009-01-01

    the relation of gene expression and chromosomal position to identify chromosomal regions of importance for early recurrence of ovarian cancer. By use of *Gene Set Enrichment Analysis*, we have ranked chromosomal regions according to their association to survival. Over-representation analysis including 1......Ovarian cancer cells exhibit complex karyotypic alterations causing deregulation of numerous genes. Some of these genes are probably causal for cancer formation and local growth, whereas others are causal for metastasis and recurrence. By using publicly available data sets, we have investigated......-4 consecutive cytogenetic bands identified regions with increased expression for chromosome 5q12-14, and a very large region of chromosome 7 with the strongest signal at 7p15-13 among tumors from short-living patients. Reduced gene expression was identified at 4q26-32, 6p12-q15, 9p21-q32, and 11p14-11. We...

  4. MreB actin-mediated segregation of a specific region of a bacterial chromosome.

    Science.gov (United States)

    Gitai, Zemer; Dye, Natalie Anne; Reisenauer, Ann; Wachi, Masaaki; Shapiro, Lucy

    2005-02-11

    Faithful chromosome segregation is an essential component of cell division in all organisms. The eukaryotic mitotic machinery uses the cytoskeleton to move specific chromosomal regions. To investigate the potential role of the actin-like MreB protein in bacterial chromosome segregation, we first demonstrate that MreB is the direct target of the small molecule A22. We then demonstrate that A22 completely blocks the movement of newly replicated loci near the origin of replication but has no qualitative or quantitative effect on the segregation of other loci if added after origin segregation. MreB selectively interacts, directly or indirectly, with origin-proximal regions of the chromosome, arguing that the origin-proximal region segregates via an MreB-dependent mechanism not used by the rest of the chromosome.

  5. Interstitial duplications of chromosome region 15q11q13 : Clinical and molecular characterization

    NARCIS (Netherlands)

    Repetto, GR; White, LM; Bader, PJ; Johnson, D; Knoll, JHM

    1998-01-01

    Duplications of chromosome region 15q11q13 often occur as a supernumerary chromosome 15. Less frequently they occur as interstitial duplications [dup(15)]. We describe the clinical and molecular characteristics of three patients with de novo dup(15). The patients, two males and one female (ages 3-21

  6. Control of bacterial chromosome replication by non-coding regions outside the origin

    DEFF Research Database (Denmark)

    Frimodt-Møller, Jakob; Charbon, Godefroid; Løbner-Olesen, Anders

    2017-01-01

    Chromosome replication in Eubacteria is initiated by initiator protein(s) binding to specific sites within the replication origin, oriC. Recently, initiator protein binding to chromosomal regions outside the origin has attracted renewed attention; as such binding sites contribute to control the f...

  7. Interstitial duplications of chromosome region 15q11q13 : Clinical and molecular characterization

    NARCIS (Netherlands)

    Repetto, GR; White, LM; Bader, PJ; Johnson, D; Knoll, JHM

    1998-01-01

    Duplications of chromosome region 15q11q13 often occur as a supernumerary chromosome 15. Less frequently they occur as interstitial duplications [dup(15)]. We describe the clinical and molecular characteristics of three patients with de novo dup(15). The patients, two males and one female (ages 3-21

  8. 45S rDNA regions are chromosome fragile sites expressed as gaps in vitro on metaphase chromosomes of root-tip meristematic cells in Lolium spp.

    Directory of Open Access Journals (Sweden)

    Jing Huang

    Full Text Available BACKGROUND: In humans, chromosome fragile sites are regions that are especially prone to forming non-staining gaps, constrictions or breaks in one or both of the chromatids on metaphase chromosomes either spontaneously or following partial inhibition of DNA synthesis and have been well identified. So far, no plant chromosome fragile sites similar to those in human chromosomes have been reported. METHODS AND RESULTS: During the course of cytological mapping of rDNA on ryegrass chromosomes, we found that the number of chromosomes plus chromosome fragments was often more than the expected 14 in most cells for Lolium perenne L. cv. Player by close cytological examination using a routine chromosome preparation procedure. Further fluorescent in situ hybridization (FISH using 45S rDNA as a probe indicated that the root-tip cells having more than a 14-chromosome plus chromosome fragment count were a result of chromosome breakage or gap formation in vitro (referred to as chromosome lesions at 45S rDNA sites, and 86% of the cells exhibited chromosome breaks or gaps and all occurred at the sites of 45S rDNA in Lolium perenne L. cv. Player, as well as in L. multiflorum Lam. cv. Top One. Chromatin depletion or decondensation occurred at various locations within the 45S rDNA regions, suggesting heterogeneity of lesions of 45S rDNA sites with respect to their position within the rDNA region. CONCLUSIONS: The chromosome lesions observed in this study are very similar cytologically to that of fragile sites observed in human chromosomes, and thus we conclude that the high frequency of chromosome lesions in vitro in Lolium species is the result of the expression of 45S rDNA fragile sites. Possible causes for the spontaneous expression of fragile sites and their potential biological significance are discussed.

  9. The terminal region of the E. coli chromosome localises at the periphery of the nucleoid

    Directory of Open Access Journals (Sweden)

    Stouf Mathieu

    2011-02-01

    Full Text Available Abstract Background Bacterial chromosomes are organised into a compact and dynamic structures termed nucleoids. Cytological studies in model rod-shaped bacteria show that the different regions of the chromosome display distinct and specific sub-cellular positioning and choreographies during the course of the cell cycle. The localisation of chromosome loci along the length of the cell has been described. However, positioning of loci across the width of the cell has not been determined. Results Here, we show that it is possible to assess the mean positioning of chromosomal loci across the width of the cell using two-dimension images from wide-field fluorescence microscopy. Observed apparent distributions of fluorescent-tagged loci of the E. coli chromosome along the cell diameter were compared with simulated distributions calculated using a range of cell width positioning models. Using this method, we detected the migration of chromosome loci towards the cell periphery induced by production of the bacteriophage T4 Ndd protein. In the absence of Ndd production, loci outside the replication terminus were located either randomly along the nucleoid width or towards the cell centre whereas loci inside the replication terminus were located at the periphery of the nucleoid in contrast to other loci. Conclusions Our approach allows to reliably observing the positioning of chromosome loci along the width of E. coli cells. The terminal region of the chromosome is preferentially located at the periphery of the nucleoid consistent with its specific roles in chromosome organisation and dynamics.

  10. Chromosomal anomalies: The experience of the Congenital Anomalies Registry of the Valencia Region

    National Research Council Canada - National Science Library

    Gimeno-Martos, S; Cavero-Carbonell, C; López-Maside, A; Bosch-Sánchez, S; Martos-Jiménez, C; Zurriaga, O

    2016-01-01

    ...) in the Valencia Region, in less than one year olds, during the period 2007-2011. Live births, still births and termination of pregnancy due to foetal anomaly between 2007 and 2011 with chromosomal CA...

  11. Regional deletion and amplification on chromosome 6 in a uveal melanoma case without abnormalities on chromosomes 1p, 3 and 8.

    Science.gov (United States)

    van Gils, Walter; Kilic, Emine; Brüggenwirth, Hennie T; Vaarwater, Jolanda; Verbiest, Michael M; Beverloo, Berna; van Til-Berg, Marjan E; Paridaens, Dion; Luyten, Gregorius P; de Klein, Annelies

    2008-02-01

    Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Loss of the long arm and gain of the short arm of chromosome 6 are frequently observed chromosomal aberrations in UM, together with loss of chromosome 1p36, loss of chromosome 3 and gain of chromosome 8. This suggests the presence of one or more oncogenes on 6p and tumor suppressor genes at 6q that are involved in UM development. Both regions, however, have not been well defined yet. Furthermore in other neoplasms gain of 6p and loss of 6q are frequently occurring events. In this case report, we describe the delineation of a partial gain on chromosome 6p and a partial deletion on 6q in a UM with the objective to pinpoint smaller candidate regions on chromosome 6 involved in UM development. Conventional cytogenetics, comparative genomic hybridization (CGH) and fluorescence in-situ hybridization (FISH) were used to delineate regions of loss and gain on chromosome 6 in this UM patient. With conventional cytogenetics a deleted region was found on chromosome 6q that was further delineated to a region ranging from 6q16.1 to 6q22 using CGH and FISH. A region of gain from 6pter to 6p21.2 was also demarcated with CGH and FISH. No other deletions or amplifications on recurrently involved chromosomes were found in this patient. This study indicates the presence of one or more tumor suppressor genes on chromosomal region 6q16.1-6q22 and the presence of one or more oncogenes on chromosomal region 6pter-6p21.2, which are likely to be important in UM and other tumors.

  12. Narrowing the genetic interval and yeast artificial chromosome map in the branchio-oto-renal region on chromosome 8q

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Shrawan; Kimberling, W.J.; Pinnt, J. [Boys Town National Research Hospital, Omaha, NE (United States)] [and others

    1996-01-01

    Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder characterized by branchial abnormality, hearing loss, and renal anomalies. Recently, the disease gene has been localized to chromosome 8q. Here, we report genetic studies that further refine the disease gene region to a smaller interval and identify several YACs from the critical region. We studied two large, clinically well-characterized BOR families with a set of 13 polymorphic markers spanning the D8S165-D8S275 interval from the chromosome 8q region. Based on multipoint analysis, the highest likelihood for the location of the BOR gene is between markers D8S543 and D8S530, a distance of about 2 cM. YACs that map in the BOR critical region have been identified and characterized by fluorescence in situ hybridization and pulsed-field gel electrophoresis. A YAC contig, based on the STS content map, that covers a minimum of 4 Mb of human DNA in the critical region of BOR is assembled. This lays the groundwork for the construction of a transcriptional map of this region and the eventual identification of genes involved in BOR syndrome. 40 refs., 4 figs., 1 tab.

  13. A new region of conservation is defined between human and mouse X chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Dinulos, M.B.; Disteche, C.M. [Univ. of Washington, Seattle, WA (United States); Bassi, M.T. [Univ. of Siena (Italy)] [and others

    1996-07-01

    Comparative mapping of the X chromosome in eutherian mammals have revealed distinct regions of conservation as well as evolutionary rearrangements between human and mouse. Recently, we and others mapped the murine homologue of CLCN4 (Chloride channel 4) to band F4 of the X chromosome in Mus spretus but to chromosome 7 in laboratory strains. We now report the mapping of the murine homologues of APXL (Apical protein Xenopus laevis-like) and OA1 (Ocular albinism type I), two genes that are located on the human X chromosome at band p22.3 and in close proximity to CLCN4. Interestingly, Oa1 and Apxl map to bands F2-F3 in both M. spretus and the laboratory strain C57BL/6J, defining a new rearrangement between human and mouse X chromosomes. 17 refs., 2 figs., 1 tab.

  14. Enhancement of multichannel chromosome classification using a region-based classifier and vector median filtering.

    Science.gov (United States)

    Karvelis, Petros S; Fotiadis, Dimitrios I; Tsalikakis, Dimitrios G; Georgiou, Ioannis A

    2009-07-01

    Multichannel chromosome image acquisition is used for cancer diagnosis and research on genetic disorders. This type of imaging, apart from aiding the cytogeneticist in several ways, facilitates the visual detection of chromosome abnormalities. However, chromosome misclassification errors result from different factors, such as uneven hybridization, spectral overlap among fluors, and biochemical noise. In this paper, we enhance the chromosome classification accuracy by making use of a region Bayes classifier that increases the classification accuracy when compared to the already developed pixel-by-pixel classifier and by incorporating the vector median filtering approach for filtering of the image. The method is evaluated using a publicly available database that contains 183 six-channel chromosome sets of images. The overall improvement on the chromosome classification accuracy is 9.99%, compared to the pixel-by-pixel classifier without filtering. This improvement in the chromosome classification accuracy would allow subtle deoxyribonucleic acid abnormalities to be identified easily. The efficiency of the method might further improve by using features extracted from each region and a more sophisticated classifier.

  15. Integrated map of the chromosome 8p12-p21 region, a region involved in human cancers and Werner syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Imbert, A.; Chaffanet, M.; Birnbaum, D.; Pebusque, M.J. [INSERM, Marseille (France)] [and others

    1996-02-15

    This article discusses the genetic mapping of the specific region on human chromosome 8, 8p12-p21, and its implications to human hereditary cancers and diseases. The localization of disease genes such as NEFL and FGFR1 are given, accomplished using contigs which span the region of deletion involved in these hereditary diseases. 59 refs., 4 figs., 3 tabs.

  16. Frequent gene conversion events between the X and Y homologous chromosomal regions in primates

    Directory of Open Access Journals (Sweden)

    Hirai Hirohisa

    2010-07-01

    Full Text Available Abstract Background Mammalian sex-chromosomes originated from a pair of autosomes. A step-wise cessation of recombination is necessary for the proper maintenance of sex-determination and, consequently, generates a four strata structure on the X chromosome. Each stratum shows a specific per-site nucleotide sequence difference (p-distance between the X and Y chromosomes, depending on the time of recombination arrest. Stratum 4 covers the distal half of the human X chromosome short arm and the p-distance of the stratum is ~10%, on average. However, a 100-kb region, which includes KALX and VCX, in the middle of stratum 4 shows a significantly lower p-distance (1-5%, suggesting frequent sequence exchanges or gene conversions between the X and Y chromosomes in humans. To examine the evolutionary mechanism for this low p-distance region, sequences of a corresponding region including KALX/Y from seven species of non-human primates were analyzed. Results Phylogenetic analysis of this low p-distance region in humans and non-human primate species revealed that gene conversion like events have taken place at least ten times after the divergence of New World monkeys and Catarrhini (i.e., Old World monkeys and hominoids. A KALY-converted KALX allele in white-handed gibbons also suggests a possible recent gene conversion between the X and Y chromosomes. In these primate sequences, the proximal boundary of this low p-distance region is located in a LINE element shared between the X and Y chromosomes, suggesting the involvement of this element in frequent gene conversions. Together with a palindrome on the Y chromosome, a segmental palindrome structure on the X chromosome at the distal boundary near VCX, in humans and chimpanzees, may mediate frequent sequence exchanges between X and Y chromosomes. Conclusion Gene conversion events between the X and Y homologous regions have been suggested, mainly in humans. Here, we found frequent gene conversions in the

  17. Tissue-specific differences in the spatial interposition of X-chromosome and 3R chromosome regions in the malaria mosquito Anopheles messeae Fall.

    Directory of Open Access Journals (Sweden)

    Gleb Artemov

    Full Text Available Spatial organization of a chromosome in a nucleus is very important in biology but many aspects of it are still generally unresolved. We focused on tissue-specific features of chromosome architecture in closely related malaria mosquitoes, which have essential inter-specific differences in polytene chromosome attachments in nurse cells. We showed that the region responsible for X-chromosome attachment interacts with nuclear lamina stronger in nurse cells, then in salivary glands cells in Anopheles messeae Fall. The inter-tissue differences were demonstrated more convincingly in an experiment of two distinct chromosomes interposition in the nucleus space of cells from four tissues. Microdissected DNA-probes from nurse cells X-chromosome (2BC and 3R chromosomes (32D attachment regions were hybridized with intact nuclei of nurse cells, salivary gland cells, follicle epithelium cells and imaginal disсs cells in 3D-FISH experiments. We showed that only salivary gland cells and follicle epithelium cells have no statistical differences in the interposition of 2BC and 32D. Generally, the X-chromosome and 3R chromosome are located closer to each other in cells of the somatic system in comparison with nurse cells on average. The imaginal disсs cell nuclei have an intermediate arrangement of chromosome interposition, similar to other somatic cells and nurse cells. In spite of species-specific chromosome attachments there are no differences in interposition of nurse cells chromosomes in An. messeae and An. atroparvus Thiel. Nurse cells have an unusual chromosome arrangement without a chromocenter, which could be due to the special mission of generative system cells in ontogenesis and evolution.

  18. Construction of physical maps for the sex-specific regions of papaya sex chromosomes

    Directory of Open Access Journals (Sweden)

    Na Jong-Kuk

    2012-05-01

    Full Text Available Abstract Background Papaya is a major fruit crop in tropical and subtropical regions worldwide. It is trioecious with three sex forms: male, female, and hermaphrodite. Sex determination is controlled by a pair of nascent sex chromosomes with two slightly different Y chromosomes, Y for male and Yh for hermaphrodite. The sex chromosome genotypes are XY (male, XYh (hermaphrodite, and XX (female. The papaya hermaphrodite-specific Yh chromosome region (HSY is pericentromeric and heterochromatic. Physical mapping of HSY and its X counterpart is essential for sequencing these regions and uncovering the early events of sex chromosome evolution and to identify the sex determination genes for crop improvement. Results A reiterate chromosome walking strategy was applied to construct the two physical maps with three bacterial artificial chromosome (BAC libraries. The HSY physical map consists of 68 overlapped BACs on the minimum tiling path, and covers all four HSY-specific Knobs. One gap remained in the region of Knob 1, the only knob structure shared between HSY and X, due to the lack of HSY-specific sequences. This gap was filled on the physical map of the HSY corresponding region in the X chromosome. The X physical map consists of 44 BACs on the minimum tiling path with one gap remaining in the middle, due to the nature of highly repetitive sequences. This gap was filled on the HSY physical map. The borders of the non-recombining HSY were defined genetically by fine mapping using 1460 F2 individuals. The genetically defined HSY spanned approximately 8.5 Mb, whereas its X counterpart extended about 5.4 Mb including a 900 Kb region containing the Knob 1 shared by the HSY and X. The 8.5 Mb HSY corresponds to 4.5 Mb of its X counterpart, showing 4 Mb (89% DNA sequence expansion. Conclusion The 89% increase of DNA sequence in HSY indicates rapid expansion of the Yh chromosome after genetic recombination was suppressed 2–3 million years ago. The

  19. SCREENING OF PRESENCE OF EXTRA Y CHROMOSOME IN AGGRESSIVE TALL MALES OF NORTH INDIAN REGION

    Directory of Open Access Journals (Sweden)

    Balreet kaur

    2015-09-01

    Full Text Available Background: Aggression has been hypothesised with biological instinctual theory, frustration theory and social learning theory. The biological instinctual theory was based on hereditary factors and is associated with XYY syndrome. Objectives: To find out the presence of extra Y chromosome in aggressive taller males of north Indian region. Materials and Methods: Buss and Perry questionnaire was used to find out the aggression of the subjects. The height was measured with the help of metallic tape. Quinacrine dihydrochloride and Macllvaines Buffer was used to stain the buccal smear slide for the general screening of the number of Y chromosomes. The conventional metaphase was prepared for the confirmation of number of Y chromosomes and the slides were stained with giemsa. Observations: The aggression was found more in taller males and they had no extra Y chromosome. Conclusions: Extra Y chromosome may be the cause of aggression and more height in males. But in the present study of males of north Indian region no extra Y chromosome was found in aggressive and taller males.

  20. Molecular mapping of the Edwards syndrome phenotype to two noncontiguous regions on chromosome 18

    Energy Technology Data Exchange (ETDEWEB)

    Boghosian-Sell, L.; Mewar, R.; Harrison, W.; Shapiro, R.M.; Zackai, E.H.; Carey, J.; Davis-Keppen, L.; Hudgins, L.; Overhauser, J.

    1994-09-01

    In an effort to identify regions on chromosome 18 that may be critical in the appearance of the Edwards syndrome phenotype, the authors have analyzed six patients with partial duplication of chromosome 18. Four of the patients have duplications involving the distal half of 18q (18q21.1-qter) and are very mildly affected. The remaining two patients have most of 18q (18q12.1-qter) duplicated, are severely affected, and have been diagnosed with Edwards syndrome. The authors have employed FISH, using DNA probes from a chromosome 18-specific library, for the precise determination of the duplicated material in each of these patients. The clinical features and the extent of the chromosomal duplication in these patients were compared with four previously reported partial trisomy 18 patients, to identify regions of chromosome 18 that may be responsible for certain clinical features of trisomy 18. The comparative analysis confirmed that there is no single region on 18q that is sufficient to produce the trisomy 18 phenotype and identified two regions on 18q that may work in conjunction to produce the Edwards syndrome phenotype. In addition, correlative analysis indicates that duplication of 18q12.3-q22.1 may be associated with more severe mental retardation in trisomy 18 individuals. 25 refs., 3 figs., 1 tab.

  1. The evolution of vertebrate somatostatin receptors and their gene regions involves extensive chromosomal rearrangements

    Directory of Open Access Journals (Sweden)

    Ocampo Daza Daniel

    2012-11-01

    Full Text Available Abstract Background Somatostatin and its related neuroendocrine peptides have a wide variety of physiological functions that are mediated by five somatostatin receptors with gene names SSTR1-5 in mammals. To resolve their evolution in vertebrates we have investigated the SSTR genes and a large number of adjacent gene families by phylogeny and conserved synteny analyses in a broad range of vertebrate species. Results We find that the SSTRs form two families that belong to distinct paralogons. We observe not only chromosomal similarities reflecting the paralogy relationships between the SSTR-bearing chromosome regions, but also extensive rearrangements between these regions in teleost fish genomes, including fusions and translocations followed by reshuffling through intrachromosomal rearrangements. These events obscure the paralogy relationships but are still tractable thanks to the many genomes now available. We have identified a previously unrecognized SSTR subtype, SSTR6, previously misidentified as either SSTR1 or SSTR4. Conclusions Two ancestral SSTR-bearing chromosome regions were duplicated in the two basal vertebrate tetraploidizations (2R. One of these ancestral SSTR genes generated SSTR2, -3 and -5, the other gave rise to SSTR1, -4 and -6. Subsequently SSTR6 was lost in tetrapods and SSTR4 in teleosts. Our study shows that extensive chromosomal rearrangements have taken place between related chromosome regions in teleosts, but that these events can be resolved by investigating several distantly related species.

  2. Human imprinted chromosomal regions are historical hot-spots of recombination.

    Directory of Open Access Journals (Sweden)

    Ionel Sandovici

    2006-07-01

    Full Text Available Human recombination rates vary along the chromosomes as well as between the two sexes. There is growing evidence that epigenetic factors may have an important influence on recombination rates, as well as on crossover position. Using both public database analysis and wet-bench approaches, we revisited the relationship between increased rates of meiotic recombination and genome imprinting. We constructed metric linkage disequilibrium (LD maps for all human chromosomal regions known to contain one or more imprinted genes. We show that imprinted regions contain significantly more LD units (LDU and have significantly more haplotype blocks of smaller sizes than flanking nonimprinted regions. There is also an excess of hot-spots of recombination at imprinted regions, and this is likely to do with the presence of imprinted genes, per se. These findings indicate that imprinted chromosomal regions are historical "hot-spots" of recombination. We also demonstrate, by direct segregation analysis at the 11p15.5 imprinted region, that there is remarkable agreement between sites of meiotic recombination and steps in LD maps. Although the increase in LDU/Megabase at imprinted regions is not associated with any significant enrichment for any particular sequence class, major sequence determinants of recombination rates seem to differ between imprinted and control regions. Interestingly, fine-mapping of recombination events within the most male meiosis-specific recombination hot-spot of Chromosome 11p15.5 indicates that many events may occur within or directly adjacent to regions that are differentially methylated in somatic cells. Taken together, these findings support the involvement of a combination of specific DNA sequences and epigenetic factors as major determinants of hot-spots of recombination at imprinted chromosomal regions.

  3. Convergent evolution of chromosomal sex-determining regions in the animal and fungal kingdoms.

    Science.gov (United States)

    Fraser, James A; Diezmann, Stephanie; Subaran, Ryan L; Allen, Andria; Lengeler, Klaus B; Dietrich, Fred S; Heitman, Joseph

    2004-12-01

    Sexual identity is governed by sex chromosomes in plants and animals, and by mating type (MAT) loci in fungi. Comparative analysis of the MAT locus from a species cluster of the human fungal pathogen Cryptococcus revealed sequential evolutionary events that fashioned this large, highly unusual region. We hypothesize that MAT evolved via four main steps, beginning with acquisition of genes into two unlinked sex-determining regions, forming independent gene clusters that then fused via chromosomal translocation. A transitional tripolar intermediate state then converted to a bipolar system via gene conversion or recombination between the linked and unlinked sex-determining regions. MAT was subsequently subjected to intra- and interallelic gene conversion and inversions that suppress recombination. These events resemble those that shaped mammalian sex chromosomes, illustrating convergent evolution in sex-determining structures in the animal and fungal kingdoms.

  4. Localization of the tight junction protein gene TJP1 to human chromosome 15q13, distal to the Prader-Willi/Angelman region, and to mouse chromosome 7

    Energy Technology Data Exchange (ETDEWEB)

    Mohandas, T.K. [Darthmouth-Hitchcock Medical Center, Lebanon, NH (United States); Chen, X.N.; Korenberg, J.R. [UCLA School of Medicine, Los Angeles, CA (United States)] [and others

    1995-12-10

    The gene encoding the tight junction (zonula occludens) protein, TJP1, was mapped to human chromosome 15q13 by fluorescence in situ hybridization (FISH) using a cDNA probe. The Jackson Laboratory backcross DNA panel derived from the cross (C57BL/6JEi X SPRET/Ei) F1 females X SPRET/Ei males was used to map the mouse Tjp1 to chromosome 7 near position 30 on the Chromosome Committee Map, a region with conserved homology to human chromosome 15q13. FISH studies on metaphases from patients with the Prader-Willi (PWS) or the Angelman syndrome (AS) showed that TJP1 maps close but distal to the PWS/AS chromosome region. 13 refs., 2 figs.

  5. Copy number variations of chromosome 16p13.1 region associated with schizophrenia

    DEFF Research Database (Denmark)

    Ingason, A; Rujescu, D; Cichon, S

    2011-01-01

    Deletions and reciprocal duplications of the chromosome 16p13.1 region have recently been reported in several cases of autism and mental retardation (MR). As genomic copy number variants found in these two disorders may also associate with schizophrenia, we examined 4345 schizophrenia patients an...... disorder and dyslexia. Candidate genes in the region include NTAN1 and NDE1. We conclude that duplications and perhaps also deletions of chromosome 16p13.1, previously reported to be associated with autism and MR, also confer risk of schizophrenia....

  6. Detection of chromosomal regions showing differential gene expression in human skeletal muscle and in alveolar rhabdomyosarcoma

    Directory of Open Access Journals (Sweden)

    Bortoluzzi Stefania

    2004-06-01

    Full Text Available Abstract Background Rhabdomyosarcoma is a relatively common tumour of the soft tissue, probably due to regulatory disruption of growth and differentiation of skeletal muscle stem cells. Identification of genes differentially expressed in normal skeletal muscle and in rhabdomyosarcoma may help in understanding mechanisms of tumour development, in discovering diagnostic and prognostic markers and in identifying novel targets for drug therapy. Results A Perl-code web client was developed to automatically obtain genome map positions of large sets of genes. The software, based on automatic search on Human Genome Browser by sequence alignment, only requires availability of a single transcribed sequence for each gene. In this way, we obtained tissue-specific chromosomal maps of genes expressed in rhabdomyosarcoma or skeletal muscle. Subsequently, Perl software was developed to calculate gene density along chromosomes, by using a sliding window. Thirty-three chromosomal regions harbouring genes mostly expressed in rhabdomyosarcoma were identified. Similarly, 48 chromosomal regions were detected including genes possibly related to function of differentiated skeletal muscle, but silenced in rhabdomyosarcoma. Conclusion In this study we developed a method and the associated software for the comparative analysis of genomic expression in tissues and we identified chromosomal segments showing differential gene expression in human skeletal muscle and in alveolar rhabdomyosarcoma, appearing as candidate regions for harbouring genes involved in origin of alveolar rhabdomyosarcoma representing possible targets for drug treatment and/or development of tumor markers.

  7. Distal 5q trisomy resulting from an X;5 translocation detected by chromosome painting.

    Science.gov (United States)

    Abuelo, D N; Ahsanuddin, A N; Mark, H F

    2000-10-23

    We describe the case of a 13-year-old girl with an apparently de novo unbalanced translocation resulting in the presence of additional chromosomal material on the short arm of one X chromosome, which was detected by conventional G-banding studies. Fluorescence in situ hybridization (FISH) using the Chromoprobe Multiprobe-M protocol confirmed that the additional chromosomal material originated from chromosome 5. The karyotype of this patient is now established to be 46,X,der(X) t(X;5)(p22.3;q33), with a deletion of Xp22.3-pter and partial trisomy of 5q33-qter. The distal 5q trisomy genotype has been associated with clinical signs that include growth and mental retardation, eczema, craniofacial anomalies, and malformations of heart, lungs, abdomen, limbs, and genitalia. Our patient also has short stature, a prominent nasal bridge, a flat philtrum, a thin upper lip, dental caries, and limb and cardiac malformations, but she appears to be mildly affected compared with previously reported cases. This is the first case of distal 5q trisomy arising from a translocation with the X chromosome. Replication studies on this patient show that the derivative t(X;5) chromosome is late replicating in almost all cells examined, which indicates that this chromosome is preferentially inactivated. However, the translocated segment of chromosome 5 appears to be early replicating, which implies that the trisomic 5q segment is transcriptionally active. We cannot determine from these studies whether all or only some genes in this segment are expressed, but this patient's relatively mild clinical signs suggest that the critical region(s) that contribute to the distal 5q trisomy phenotype are at least partly suppressed. A review of other patients with X-chromosome translocations indicates that many but not all of them also have attenuated phenotypes. The mechanism of inactivation of autosomal material attached to the X chromosome is complex, with varying effects on the phenotype of the

  8. Variations of chromosomal structures in Caluromys philander (Didelphimorphia: Didelphidae) from the Amazon region.

    Science.gov (United States)

    Souza, Erica Martinha Silva de; Faresin e Silva, Carlos Eduardo; Eler, Eduardo Schmidt; Silva, Maria Nazareth F da; Feldberg, Eliana

    2013-03-01

    Caluromys is considered to be one of the most ancient genera of extant marsupials and is positioned among the basal taxa of the family Didelphidae. At least two species occur in Brazil, C. philander and C. lanatus, both of which have 2n = 14 chromosomes. For the first time, we present evidence of an intrapopulation polymorphism of the sexual chromosome pair in C. philander females from the Central Amazon region. Detailed cytogenetic results of animals from three localities on the Amazon region were analyzed using classical cytogenetics (NOR, C-Band and G-Band) and molecular techniques (18S rDNA and telomere probes). Similar to other conspecific individuals, the diploid number of these animals is 2n = 14, and their fundamental number is 24, with NOR present on the 6th autosomal pair. The X chromosome presented variation detectable by G banding, suggesting a pericentric inversion.

  9. Differentially methylated regions in maternal and paternal uniparental disomy for chromosome 7.

    Science.gov (United States)

    Hannula-Jouppi, Katariina; Muurinen, Mari; Lipsanen-Nyman, Marita; Reinius, Lovisa E; Ezer, Sini; Greco, Dario; Kere, Juha

    2014-03-01

    DNA methylation is a hallmark of genomic imprinting and differentially methylated regions (DMRs) are found near and in imprinted genes. Imprinted genes are expressed only from the maternal or paternal allele and their normal balance can be disrupted by uniparental disomy (UPD), the inheritance of both chromosomes of a chromosome pair exclusively from only either the mother or the father. Maternal UPD for chromosome 7 (matUPD7) results in Silver-Russell syndrome (SRS) with typical features and growth retardation, but no gene has been conclusively implicated in SRS. In order to identify novel DMRs and putative imprinted genes on chromosome 7, we analyzed eight matUPD7 patients, a segmental matUPD7q31-qter, a rare patUPD7 case and ten controls on the Infinium HumanMethylation450K BeadChip with 30 017 CpG methylation probes for chromosome 7. Genome-scale analysis showed highly significant clustering of DMRs only on chromosome 7, including the known imprinted loci GRB10, SGCE/PEG10, and PEG/MEST. We found ten novel DMRs on chromosome 7, two DMRs for the predicted imprinted genes HOXA4 and GLI3 and one for the disputed imprinted gene PON1. Quantitative RT-PCR on blood RNA samples comparing matUPD7, patUPD7, and controls showed differential expression for three genes with novel DMRs, HOXA4, GLI3, and SVOPL. Allele specific expression analysis confirmed maternal only expression of SVOPL and imprinting of HOXA4 was supported by monoallelic expression. These results present the first comprehensive map of parent-of-origin specific DMRs on human chromosome 7, suggesting many new imprinted sites.

  10. Long-range restriction map of the terminal part of the short arm of the human X chromosome

    Energy Technology Data Exchange (ETDEWEB)

    Petit, C.; Levilliers, J.; Weissenbach, J. (Institut Pasteur, Paris (France))

    1990-05-01

    The terminal part of the short arm of the human X chromosome has been mapped by pulsed-field gel electrophoresis (PFGE). The map, representing the distal two-thirds of Xp22.3 spans a total of 10,000 kilobases (kb) from Xpter to the DXS143 locus. A comparison with linkage data indicates that 1 centimorgan (cM) in this region corresponds to about 600 kb. CpG islands were essentially concentrated in the 1,500 kb immediately proximal to the pseudoautosomal boundary. Several loci, including the gene encoding steroid sulfatase (STS) and the loci for the X-linked recessive form of chondrodysplasia punctata (CDPX) and for Kallmann syndrome (KAL) have been placed relative to the Xp telomere. CDPX is located between 2,650 and 5,550 kb from Xpter, and STS is located between 7,250 and 7,830 kb from Xpter. KAL maps to an interval of 350 kb between 8,600 and 8,950 kb from the telomere. The X-chromosomal breakpoints of a high proportion of XX males resulting from X-Y interchange cluster to a 920-kb region proximal and close to the pseudoautosomal boundary.

  11. Copy number variations of chromosome 16p13.1 region associated with schizophrenia

    NARCIS (Netherlands)

    Ingason, A.; Rujescu, D.; Cichon, S.; Sigurdsson, E.; Sigmundsson, T.; Pietilainen, O.P.H.; Buizer-Voskamp, J.E.; Strengman, E.; Francks, C.; Muglia, P.; Gylfason, A.; Gustafsson, O.; Olason, P.I.; Steinberg, S.; Hansen, T.; Jakobsen, K.D.; Rasmussen, H.B.; Giegling, I.; Moller, H.J.; Hartmann, A.; Crombie, C.; Fraser, G.; Walker, N.; Lonnqvist, J.; Suvisaari, J.; Tuulio-Henriksson, A.; Bramon, E.; Kiemeney, L.A.L.M.; Franke, B.; Murray, R.; Vassos, E.; Toulopoulou, T.; Muhleisen, T.W.; Tosato, S.; Ruggeri, M.; Djurovic, S.; Andreassen, O.A.; Zhang, Z.; Werge, T.; Ophoff, R.A.; Rietschel, M.; Nothen, M.M.; Petursson, H.; Stefansson, H.; Peltonen, L.; Collier, D.; Stefansson, K.; St Clair, D.M.

    2011-01-01

    Deletions and reciprocal duplications of the chromosome 16p13.1 region have recently been reported in several cases of autism and mental retardation (MR). As genomic copy number variants found in these two disorders may also associate with schizophrenia, we examined 4345 schizophrenia patients and 3

  12. Gene recovery microdissection (GRM) a process for producing chromosome region-specific libraries of expressed genes

    Energy Technology Data Exchange (ETDEWEB)

    Christian, A T; Coleman, M A; Tucker, J D

    2001-02-08

    Gene Recovery Microdissection (GRM) is a unique and cost-effective process for producing chromosome region-specific libraries of expressed genes. It accelerates the pace, reduces the cost, and extends the capabilities of functional genomic research, the means by which scientists will put to life-saving, life-enhancing use their knowledge of any plant or animal genome.

  13. Allelic gains and losses in distinct regions of chromosome 6 in gastric carcinoma

    NARCIS (Netherlands)

    Carvalho, B; van der Veen, AY; Gartner, F; Carneiro, F; Seruca, R; Buys, CHCM; Kok, K

    2001-01-01

    In gastric cancer, alterations in the long arm of chromosome 6 are a frequent event. Two regions of heterozygous loss have been described: 6q16.3 similar to 6q23 and 6q26 similar to 6q27. We have evaluated by microsatellite and FISH analyses the 6q status of three cell lines that we established from

  14. A genetic linkage map of the diplosporous chromosomal region in Taraxacum officinale (common dandelion; Asteracaea)

    NARCIS (Netherlands)

    Vijverberg, K.; Hulst, van der R.G.M.; Lindhout, W.H.; Dijk, P.J.

    2004-01-01

    In this study, we mapped the diplosporous chromosomal region in Taraxacum officinale, by using amplified fragment length polymorphism technology (AFLP) in 73 plants from a segregating population. Taraxacum serves as a model system to investigate the genetics, ecology, and evolution of apomixis. The

  15. A genetic linkage map of the diplosporous chromosomal region in Taraxacum officinale (common dandelion; Asteraceae)

    NARCIS (Netherlands)

    Vijverberg, Kitty; van der Hulst, R.G.M.; Lindhout, P.; Van Dijk, P.J.

    2004-01-01

    In this study, we mapped the diplosporous chromosomal region in Taraxacum officinale, by using amplified fragment length polymorphism technology (AFLP) in 73 plants from a segregating population. Taraxacum serves as a model system to investigate the genetics, ecology, and evolution of apomixis. The

  16. A genetic linkage map of the diplosporous chromosomal region in Taraxacum officinale (common dandelion; Asteracaea)

    NARCIS (Netherlands)

    Vijverberg, K.; Hulst, van der R.G.M.; Lindhout, W.H.; Dijk, P.J.

    2004-01-01

    In this study, we mapped the diplosporous chromosomal region in Taraxacum officinale, by using amplified fragment length polymorphism technology (AFLP) in 73 plants from a segregating population. Taraxacum serves as a model system to investigate the genetics, ecology, and evolution of apomixis. The

  17. A genetic linkage map of the diplosporous chromosomal region in Taraxacum officinale (common dandelion; Asteraceae)

    NARCIS (Netherlands)

    Vijverberg, Kitty; van der Hulst, R.G.M.; Lindhout, P.; Van Dijk, P.J.

    2004-01-01

    In this study, we mapped the diplosporous chromosomal region in Taraxacum officinale, by using amplified fragment length polymorphism technology (AFLP) in 73 plants from a segregating population. Taraxacum serves as a model system to investigate the genetics, ecology, and evolution of apomixis. The

  18. Allelic gains and losses in distinct regions of chromosome 6 in gastric carcinoma

    NARCIS (Netherlands)

    Carvalho, B; van der Veen, AY; Gartner, F; Carneiro, F; Seruca, R; Buys, CHCM; Kok, K

    2001-01-01

    In gastric cancer, alterations in the long arm of chromosome 6 are a frequent event. Two regions of heterozygous loss have been described: 6q16.3 similar to 6q23 and 6q26 similar to 6q27. We have evaluated by microsatellite and FISH analyses the 6q status of three cell lines that we established from

  19. Fine Mapping and Evolution of a QTL Region on Cattle Chromosome 3

    Science.gov (United States)

    Donthu, Ravikiran

    2009-01-01

    The goal of my dissertation was to fine map the milk yield and composition quantitative trait loci (QTL) mapped to cattle chromosome 3 (BTA3) by Heyen et al. (1999) and to identify candidate genes affecting these traits. To accomplish this, the region between "BL41" and "TGLA263" was mapped to the cattle genome sequence assembly Btau 3.1 and a…

  20. The gene for calcium-modulating cyclophilin ligand (CAMLG) is located on human Chromosome 5q23 and a syntenic region of mouse chromosome 13

    Energy Technology Data Exchange (ETDEWEB)

    Bram, R.J.; Valentine, V.; Shapiro, D.N. [St. Jude Children`s Research Hospital, Memphis, TN (United States)]|[Univ. of Tennessee, Memphis, TN (United States)] [and others

    1996-01-15

    The CAMLG gene encodes a novel cyclophilin B-binding protein called calcium-modulating cyclophilin ligand, which appears to be involved in the regulation of calcium signaling in T lymphocytes and other cells. The murine homolog, Caml, was localized by interspecific backcross analysis in the middle of chromosome 13. By fluorescence in situ hybridization, this gene was localized to human chromosome 5 in a region (q23) known to be syntenic to mouse chromosome 13. These results provide further evidence supporting the extensive homology between human chromosome 5q and mouse chromosome 13. In addition, the results will provide a basis for further evaluation of cytogenetic anomalies that may contribute to inherited defects in calcium signaling or immune system function. 15 refs., 2 figs.

  1. [Chromosomal anomalies: The experience of the Congenital Anomalies Registry of the Valencia Region].

    Science.gov (United States)

    Gimeno-Martos, S; Cavero-Carbonell, C; López-Maside, A; Bosch-Sánchez, S; Martos-Jiménez, C; Zurriaga, O

    2016-04-01

    To describe the temporal trend and distribution of chromosomal congenital abnormalities (CA) in the Valencia Region, in less than one year olds, during the period 2007-2011. Live births, still births and termination of pregnancy due to foetal anomaly between 2007 and 2011 with chromosomal CA (Q90-Q99.9 codes of the 10th International Classification of Diseases -British Paediatric Association) were selected from the CA population-based Registry of Valencia Region The prevalence per 10,000 births for the chromosomal CA and for the different types of chromosomal syndromes with 95% confidence intervals was calculated. The analysis was performed by calculating prevalences and data were compared using Pearson Chi-squared test. A total of 895 cases were found, representing a prevalence of 33.5 per 10,000 births (95% CI: 31.0-35.9), highlighting five syndromes: Down's, Edward's, Patau, Turner and Klinefelter. The prevalence of chromosomal CA and Down's syndrome were stable over the period, except in 2010. Down's was the most frequent chromosomal CA (67% of the cases), and the most frequent termination of pregnancy type was for foetal anomaly (69%). Cardiac heart defects represented 70.3% of the associated congenital anomalies. Mothers of children with chromosomal CA were mainly Spanish (73.3%). The age group of mothers over 39 years had a higher prevalence (133.0 per 10,000 births). The province of Castellón had the highest prevalence, 39.1 per 10,000 births. The prevalence has remained stable over the five years, excluding the significant decline in 2010, for chromosomal CA detected and two of the major syndromes. The chromosomal CA are an important public health problem as they represent 15% of all CA identified in the Valencia Region, and agrees with the European data. Copyright © 2015 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  2. Characterization of a rice variety with high hydraulic conductance and identification of the chromosome region responsible using chromosome segment substitution lines.

    Science.gov (United States)

    Adachi, Shunsuke; Tsuru, Yukiko; Kondo, Motohiko; Yamamoto, Toshio; Arai-Sanoh, Yumiko; Ando, Tsuyu; Ookawa, Taiichiro; Yano, Masahiro; Hirasawa, Tadashi

    2010-11-01

    The rate of photosynthesis in paddy rice often decreases at noon on sunny days because of water stress, even under submerged conditions. Maintenance of higher rates of photosynthesis during the day might improve both yield and dry matter production in paddy rice. A high-yielding indica variety, 'Habataki', maintains a high rate of leaf photosynthesis during the daytime because of the higher hydraulic conductance from roots to leaves than in the standard japonica variety 'Sasanishiki'. This research was conducted to characterize the trait responsible for the higher hydraulic conductance in 'Habataki' and identified a chromosome region for the high hydraulic conductance. Hydraulic conductance to passive water transport and to osmotic water transport was determined for plants under intense transpiration and for plants without transpiration, respectively. The varietal difference in hydraulic conductance was examined with respect to root surface area and hydraulic conductivity (hydraulic conductance per root surface area, L(p)). To identify the chromosome region responsible for higher hydraulic conductance, chromosome segment substitution lines (CSSLs) derived from a cross between 'Sasanishiki' and 'Habataki' were used. The significantly higher hydraulic conductance resulted from the larger root surface area not from L(p) in 'Habataki'. A chromosome region associated with the elevated hydraulic conductance was detected between RM3916 and RM2431 on the long arm of chromosome 4. The CSSL, in which this region was substituted with the 'Habataki' chromosome segment in the 'Sasanishiki' background, had a larger root mass than 'Sasanishiki'. The trait for increasing plant hydraulic conductance and, therefore, maintaining the higher rate of leaf photosynthesis under the conditions of intense transpiration in 'Habataki' was identified, and it was estimated that there is at least one chromosome region for the trait located on chromosome 4.

  3. Genomic structure and paralogous regions of the inversion breakpoint occurring between human chromosome 3p12.3 and orangutan chromosome 2.

    Science.gov (United States)

    Yue, Y; Grossmann, B; Tsend-Ayush, E; Grützner, F; Ferguson-Smith, M A; Yang, F; Haaf, T

    2005-01-01

    Intrachromosomal duplications play a significant role in human genome pathology and evolution. To better understand the molecular basis of evolutionary chromosome rearrangements, we performed molecular cytogenetic and sequence analyses of the breakpoint region that distinguishes human chromosome 3p12.3 and orangutan chromosome 2. FISH with region-specific BAC clones demonstrated that the breakpoint-flanking sequences are duplicated intrachromosomally on orangutan 2 and human 3q21 as well as at many pericentromeric and subtelomeric sites throughout the genomes. Breakage and rearrangement of the human 3p12.3-homologous region in the orangutan lineage were associated with a partial loss of duplicated sequences in the breakpoint region. Consistent with our FISH mapping results, computational analysis of the human chromosome 3 genomic sequence revealed three 3p12.3-paralogous sequence blocks on human chromosome 3q21 and smaller blocks on the short arm end 3p26-->p25. This is consistent with the view that sequences from an ancestral site at 3q21 were duplicated at 3p12.3 in a common ancestor of orangutan and humans. Our results show that evolutionary chromosome rearrangements are associated with microduplications and microdeletions, contributing to the DNA differences between closely related species. Copyright (c) 2005 S. Karger AG, Basel.

  4. Evolution of the DAZ gene and the AZFc region on primate Y chromosomes

    Directory of Open Access Journals (Sweden)

    Yu Jane-Fang

    2008-03-01

    Full Text Available Abstract Background The Azoospermia Factor c (AZFc region of the human Y chromosome is a unique product of segmental duplication. It consists almost entirely of very long amplicons, represented by different colors, and is frequently deleted in subfertile men. Most of the AZFc amplicons have high sequence similarity with autosomal segments, indicating recent duplication and transposition to the Y chromosome. The Deleted in Azoospermia (DAZ gene within the red-amplicon arose from an ancestral autosomal DAZ-like (DAZL gene. It varies significantly between different men regarding to its copy number and the numbers of RNA recognition motif and DAZ repeat it encodes. We used Southern analyses to study the evolution of DAZ and AZFc amplicons on the Y chromosomes of primates. Results The Old World monkey rhesus macaque has only one DAZ gene. In contrast, the great apes have multiple copies of DAZ, ranging from 2 copies in bonobos and gorillas to at least 6 copies in orangutans, and these DAZ genes have polymorphic structures similar to those of their human counterparts. Sequences homologous to the various AZFc amplicons are present on the Y chromosomes of some but not all primates, indicating that they arrived on the Y chromosome at different times during primate evolution. Conclusion The duplication and transposition of AZFc amplicons to the human Y chromosome occurred in three waves, i.e., after the branching of the New World monkey, the gorilla, and the chimpanzee/bonobo lineages, respectively. The red-amplicon, one of the first to arrive on the Y chromosome, amplified by inverted duplication followed by direct duplication after the separation of the Old World monkey and the great ape lineages. Subsequent duplication/deletion in the various lineages gave rise to a spectrum of DAZ gene structure and copy number found in today's great apes.

  5. Nucleoporin translocated promoter region (Tpr) associates with dynein complex, preventing chromosome lagging formation during mitosis.

    Science.gov (United States)

    Nakano, Hiroshi; Funasaka, Tatsuyoshi; Hashizume, Chieko; Wong, Richard W

    2010-04-01

    Gain or loss of whole chromosomes is often observed in cancer cells and is thought to be due to aberrant chromosome segregation during mitosis. Proper chromosome segregation depends on a faithful interaction between spindle microtubules and kinetochores. Several components of the nuclear pore complex/nucleoporins play critical roles in orchestrating the rapid remodeling events that occur during mitosis. Our recent studies revealed that the nucleoporin, Rae1, plays critical roles in maintaining spindle bipolarity. Here, we show association of another nucleoporin, termed Tpr (translocated promoter region), with the molecular motors dynein and dynactin, which both orchestrate with the spindle checkpoints Mad1 and Mad2 during cell division. Overexpression of Tpr enhanced multinucleated cell formation. RNA interference-mediated knockdown of Tpr caused a severe lagging chromosome phenotype and disrupted spindle checkpoint proteins expression and localization. Next, we performed a series of rescue and dominant negative experiments to confirm that Tpr orchestrates proper chromosome segregation through interaction with dynein light chain. Our data indicate that Tpr functions as a spatial and temporal regulator of spindle checkpoints, ensuring the efficient recruitment of checkpoint proteins to the molecular motor dynein to promote proper anaphase formation.

  6. Prenatal diagnosis of chromosome 15 abnormalities in the Prader-Willi/Angelman syndrome region by traditional and molecular cytogenetics

    Energy Technology Data Exchange (ETDEWEB)

    Toth-Fejel, S.; Magenis, R.E.; Leff, S. [Oregon Health Sciences Univ., Portland, OR (United States)] [and others

    1995-02-13

    With improvements in culturing and banding techniques, amniotic fluid studies now achieve a level of resolution at which the Prader-Willi syndrome (PWS) and Angelman syndrome (AS) region may be questioned. Chromosome 15 heteromorphisms, detected with Q- and R-banding and used in conjunction with PWS/AS region-specific probes, can confirm a chromosome deletion and establish origin to predict the clinical outcome. We report four de novo cases of an abnormal-appearing chromosome 15 in amniotic fluid samples referred for advanced maternal age or a history of a previous chromosomally abnormal child. The chromosomes were characterized using G-, Q-, and R-banding, as well as isotopic and fluorescent in situ hybridization of DNA probes specific for the proximal chromosome 15 long arm. In two cases, one chromosome 15 homolog showed a consistent deletion of the ONCOR PWS/AS region A and B. In the other two cases, one of which involved an inversion with one breakpoint in the PWS/AS region, all of the proximal chromosome 15 long arm DNA probes used in the in situ hybridization were present on both homologs. Clinical follow-up was not available on these samples, as in all cases the parents chose to terminate the pregnancies. These cases demonstrate the ability to prenatally diagnose chromosome 15 abnormalities associated with PWS/AS. In addition, they highlight the need for a better understanding of this region for accurate prenatal diagnosis. 41 refs., 5 figs.

  7. The size and sequence organization of the centromeric region of arabidopsis thaliana chromosome 5.

    Science.gov (United States)

    Kumekawa, N; Hosouchi, T; Tsuruoka, H; Kotani, H

    2000-12-31

    We have determined the size of the centromeric region of Arabidopsis thaliana chromosome 5, which corresponds to the genetically defined centromere by Copenhaver et al. (Science, 286, 2468-2474, 1999) on the basis of restriction analysis. As a large clone gap was present in the previously constructed contig map of the centromeric region, the restriction map of this region was constructed using Asc I, Not I, Apa I and Pme I and genomic DNA from a hypomethylated strain. The size of the centromeric region finally estimated by combination with the sequence data of cloned regions at both sides was 4.35 megabases (Mb). This value is over 2 Mb longer than those estimated in our previous work and also by Copenhaver et al. Combing this centromeric region with the physical map previously constructed, the entire length of chromosome 5 becomes 31 Mb. Although the internal moiety of the centromeric region has not been sequenced yet because of extremely high repetition, the result of sequence analysis from both sides toward the inside strongly suggests that the centromeric region is composed of the central 2.9-Mb domain consisting of mainly 180-bp repeats and Athila retrotransposons and flanking regions containing various types of transposons. On the basis of these observations, a structural model for the centromeric region is discussed.

  8. High resolution physical map of porcine chromosome 7 QTL region and comparative mapping of this region among vertebrate genomes

    Directory of Open Access Journals (Sweden)

    Demeure Olivier

    2006-01-01

    Full Text Available Abstract Background On porcine chromosome 7, the region surrounding the Major Histocompatibility Complex (MHC contains several Quantitative Trait Loci (QTL influencing many traits including growth, back fat thickness and carcass composition. Previous studies highlighted that a fragment of ~3.7 Mb is located within the Swine Leucocyte Antigen (SLA complex. Internal rearrangements of this fragment were suggested, and partial contigs had been built, but further characterization of this region and identification of all human chromosomal fragments orthologous to this porcine fragment had to be carried out. Results A whole physical map of the region was constructed by integrating Radiation Hybrid (RH mapping, BAC fingerprinting data of the INRA BAC library and anchoring BAC end sequences on the human genome. 17 genes and 2 reference microsatellites were ordered on the high resolution IMNpRH212000rad Radiation Hybrid panel. A 1000:1 framework map covering 550 cR12000 was established and a complete contig of the region was developed. New micro rearrangements were highlighted between the porcine and human genomes. A bovine RH map was also developed in this region by mapping 16 genes. Comparison of the organization of this region in pig, cattle, human, mouse, dog and chicken genomes revealed that 1 the translocation of the fragment described previously is observed only on the bovine and porcine genomes and 2 the new internal micro rearrangements are specific of the porcine genome. Conclusion We estimate that the region contains several rearrangements and covers 5.2 Mb of the porcine genome. The study of this complete BAC contig showed that human chromosomal fragments homologs of this heavily rearranged QTL region are all located in the region of HSA6 that surrounds the centromere. This work allows us to define a list of all candidate genes that could explain these QTL effects.

  9. Characterization of the OmyY1 Region on the Rainbow Trout Y Chromosome

    Directory of Open Access Journals (Sweden)

    Ruth B. Phillips

    2013-01-01

    Full Text Available We characterized the male-specific region on the Y chromosome of rainbow trout, which contains both sdY (the sex-determining gene and the male-specific genetic marker, OmyY1. Several clones containing the OmyY1 marker were screened from a BAC library from a YY clonal line and found to be part of an 800 kb BAC contig. Using fluorescence in situ hybridization (FISH, these clones were localized to the end of the short arm of the Y chromosome in rainbow trout, with an additional signal on the end of the X chromosome in many cells. We sequenced a minimum tiling path of these clones using Illumina and 454 pyrosequencing. The region is rich in transposons and rDNA, but also appears to contain several single-copy protein-coding genes. Most of these genes are also found on the X chromosome; and in several cases sex-specific SNPs in these genes were identified between the male (YY and female (XX homozygous clonal lines. Additional genes were identified by hybridization of the BACs to the cGRASP salmonid 4x44K oligo microarray. By BLASTn evaluations using hypothetical transcripts of OmyY1-linked candidate genes as query against several EST databases, we conclude at least 12 of these candidate genes are likely functional, and expressed.

  10. Characterization of the OmyY1 region on the rainbow trout Y chromosome

    Science.gov (United States)

    Phillips, Ruth B.; DeKoning, Jenefer J.; Brunelli, Joseph P.; Faber-Hammond, Joshua J.; Hansen, John D.; Christensen, Kris A.; Renn, Suzy C.P.; Thorgaard, Gary H.

    2013-01-01

    We characterized the male-specific region on the Y chromosome of rainbow trout, which contains both sdY (the sex-determining gene) and the male-specific genetic marker, OmyY1. Several clones containing the OmyY1 marker were screened from a BAC library from a YY clonal line and found to be part of an 800 kb BAC contig. Using fluorescence in situ hybridization (FISH), these clones were localized to the end of the short arm of the Y chromosome in rainbow trout, with an additional signal on the end of the X chromosome in many cells. We sequenced a minimum tiling path of these clones using Illumina and 454 pyrosequencing. The region is rich in transposons and rDNA, but also appears to contain several single-copy protein-coding genes. Most of these genes are also found on the X chromosome; and in several cases sex-specific SNPs in these genes were identified between the male (YY) and female (XX) homozygous clonal lines. Additional genes were identified by hybridization of the BACs to the cGRASP salmonid 4x44K oligo microarray. By BLASTn evaluations using hypothetical transcripts of OmyY1-linked candidate genes as query against several EST databases, we conclude at least 12 of these candidate genes are likely functional, and expressed.

  11. Fine mapping of the human pentraxin gene region on chromosome 1q23

    Energy Technology Data Exchange (ETDEWEB)

    Walsh, M.T.; Whitehead, A.S. [Univ. of Dublin (Ireland); Divane, A. [Univ. of Cambridge (United Kingdom)

    1996-12-31

    The 1q21 to 25 region of human chromosome 1 contains genes which encode proteins with immune- and inflammation-associated functions. These include the pentraxin genes, for C-reactive protein (CRP), serum amyloid P(SAP) protein (APCS), and a CRP pseudogene (CRPP1). The region of chromosome 1 containing this cluster is syntenic with distal mouse chromosome 1. We constructed an approximately 1.4 megabase yeast artificial chromosome (YAC) contig with the pentraxin genes at its core. This four-YAC contig includes other genes with immune functions including the FCER1A gene, which encodes the {alpha}-subunit of the IgE high-affinity Fc receptor and the 1F1-16 gene, an interferon-{gamma}-induced gene. In addition, it contains the histone H3F2 and H4F2 genes and the gene for erythroid {alpha}-spectrin (SPTA1). The gene order is cen.-SPTA1-H4F2-H3F2-1F1-16-CRP-CRPP1-APCS-FCERIA-tel. The contig thus consists of a cluster of genes whose products either have immunological importance, bind DNA, or both. 68 refs., 3 figs., 2 tabs.

  12. Identification of the human chromosomal region containing the iridogoniodysgenesis anomaly locus by genomic-mismatch scanning.

    Science.gov (United States)

    Mirzayans, F; Mears, A J; Guo, S W; Pearce, W G; Walter, M A

    1997-01-01

    Genome-mismatch scanning (GMS) is a new method of linkage analysis that rapidly isolates regions of identity between two genomes. DNA molecules from regions of identity by descent from two relatives are isolated based on their ability to form extended mismatch-free heteroduplexes. We have applied this rapid technology to identify the chromosomal region shared by two fifth-degree cousins with autosomal dominant iridogoniodysgenesis anomaly (IGDA), a rare ocular neurocristopathy. Markers on the short arm of human chromosome 6p were recovered, consistent with the results of conventional linkage analysis conducted in parallel, indicating linkage of IGDA to 6p25. Control markers tested on a second human chromosome were not recovered. A GMS error rate of approximately 11% was observed, well within an acceptable range for a rapid, first screening approach, especially since GMS results would be confirmed by family analysis with selected markers from the putative region of identity by descent. These results demonstrate not only the value of this technique in the rapid mapping of human genetic traits, but the first application of GMS to a multicellular organism. Images Figure 2 PMID:9245991

  13. Nucleolar organizer regions in Sittasomus griseicapillus and Lepidocolaptes angustirostris (Aves, Dendrocolaptidae: evidence of a chromosome inversion

    Directory of Open Access Journals (Sweden)

    Marcelo de Oliveira Barbosa

    2013-01-01

    Full Text Available Cytogenetic studies in birds are still scarce compared to other vertebrates. Woodcreepers (Dendrocolaptidae are part of a highly specialized group within the Suboscines of the New World. They are forest birds exclusive to the Neotropical region and similar to woodpeckers, at a comparable evolutionary stage. This paper describes for the first time the karyotypes of the Olivaceous and the Narrow-billed Woodcreeper using conventional staining with Giemsa and silver nitrate staining of the nucleolar organizer regions (Ag-NORs. Metaphases were obtained by fibular bone marrow culture. The chromosome number of the Olivaceous Woodcreeper was 2n = 82 and of the Narrow-billed Woodcreeper, 2n = 82. Ag-NORs in the largest macrochromosome pair and evidence of a chromosome inversion are described herein for the first time for this group.

  14. Computational Comparison of Human Genomic Sequence Assemblies for a Region of Chromosome 4

    OpenAIRE

    Semple, Colin; Stewart W. Morris; Porteous, David J.; Evans, Kathryn L.

    2002-01-01

    Much of the available human genomic sequence data exist in a fragmentary draft state following the completion of the initial high-volume sequencing performed by the International Human Genome Sequencing Consortium (IHGSC) and Celera Genomics (CG). We compared six draft genome assemblies over a region of chromosome 4p (D4S394–D4S403), two consecutive releases by the IHGSC at University of California, Santa Cruz (UCSC), two consecutive releases from the National Centre for Biotechnology Informa...

  15. Characterization of chromosomal regions conserved in Yersinia pseudotuberculosis and lost by Yersinia pestis.

    Science.gov (United States)

    Pouillot, Flavie; Fayolle, Corinne; Carniel, Elisabeth

    2008-10-01

    The transformation of the enteropathogenic bacterium Yersinia pseudotuberculosis into the plague bacillus, Yersinia pestis, has been accompanied by extensive genetic loss. This study focused on chromosomal regions conserved in Y. pseudotuberculosis and lost during its transformation into Y. pestis. An extensive PCR screening of 78 strains of the two species identified five regions (R1 to R5) and four open reading frames (ORFs; orf1 to orf4) that were conserved in Y. pseudotuberculosis and absent from Y. pestis. Their conservation in Y. pseudotuberculosis suggests a positive selective pressure and a role during the life cycle of this species. Attempts to delete two ORFs (orf3 and orf4) from the chromosome of strain IP32953 were unsuccessful, indicating that they are essential for its viability. The seven remaining loci were individually deleted from the IP32953 chromosome, and the ability of each mutant to grow in vitro and to kill mice upon intragastric infection was evaluated. Four loci (orf1, R2, R4, and R5) were not required for optimal growth or virulence of Y. pseudotuberculosis. In contrast, orf2, encoding a putative pseudouridylate synthase involved in RNA stability, was necessary for the optimal growth of IP32953 at 37 degrees C in a chemically defined medium (M63S). Deletion of R1, a region predicted to encode the methionine salvage pathway, altered the mutant pathogenicity, suggesting that the availability of free methionine is severely restricted in vivo. R3, a region composed mostly of genes of unknown functions, was necessary for both optimal growth of Y. pseudotuberculosis at 37 degrees C in M63S and for virulence. Therefore, despite their loss in Y. pestis, five of the nine Y. pseudotuberculosis-specific chromosomal loci studied play a role in the survival, growth, or virulence of this species.

  16. Physical mapping and YAC contig analysis of the region surrounding Xist on the mouse X chromosome.

    Science.gov (United States)

    Heard, E; Simmler, M C; Larin, Z; Rougeulle, C; Courtier, B; Lehrach, H; Avner, P

    1993-03-01

    The Xist sequence has been proposed as a potential candidate for the X-inactivation center based both on its localization within the candidate region for the X-inactivation center in man and mouse and on its unique pattern of expression from the inactive X chromosome. We have cloned 550 kb of DNA surrounding the mouse Xist sequence in contiguously overlapping YAC clones and have developed a long-range restriction map that spans almost 1 Mb of this region and includes this YAC contig. The detailed restriction map we have established provides a framework for the identification of expressed sequences other than Xist that may equally exhibit unusual expression characteristics associated with X inactivation. The presence of possible structural or methylation differences within this region between the active and inactive X chromosomes has been investigated through comparative analysis of male and female genomic DNA, and we report here the identification of certain CpG-containing restriction sites around Xist that have an interesting differential methylation status on the inactive and active X chromosomes.

  17. Genomic structure and evolution of the ancestral chromosome fusion site in 2q13-2q14.1 and paralogous regions on other human chromosomes.

    Science.gov (United States)

    Fan, Yuxin; Linardopoulou, Elena; Friedman, Cynthia; Williams, Eleanor; Trask, Barbara J

    2002-11-01

    Human chromosome 2 was formed by the head-to-head fusion of two ancestral chromosomes that remained separate in other primates. Sequences that once resided near the ends of the ancestral chromosomes are now interstitially located in 2q13-2q14.1. Portions of these sequences had duplicated to other locations prior to the fusion. Here we present analyses of the genomic structure and evolutionary history of >600 kb surrounding the fusion site and closely related sequences on other human chromosomes. Sequence blocks that closely flank the inverted arrays of degenerate telomere repeats marking the fusion site are duplicated at many, primarily subtelomeric, locations. In addition, large portions of a 168-kb centromere-proximal block are duplicated at 9pter, 9p11.2, and 9q13, with 98%-99% average sequence identity. A 67-kb block on the distal side of the fusion site is highly homologous to sequences at 22qter. A third ~100-kb segment is 96% identical to a region in 2q11.2. By integrating data on the extent and similarity of these paralogous blocks, including the presence of phylogenetically informative repetitive elements, with observations of their chromosomal distribution in nonhuman primates, we infer the order of the duplications that led to their current arrangement. Several of these duplicated blocks may be associated with breakpoints of inversions that occurred during primate evolution and of recurrent chromosome rearrangements in humans.

  18. Chromosomal protein HMG-14 gene maps to the Down syndrome region of human chromosome 21 and is overexpressed in mouse trisomy 16

    Energy Technology Data Exchange (ETDEWEB)

    Pash, J.; Popescu, N.; Matocha, M.; Rapoport, S.; Bustin, M. (National Institutes of Health, Bethesda, MD (USA))

    1990-05-01

    The gene for human high-mobility-group (HMG) chromosomal protein HMG-14 is located in region 21q22.3, a region associated with the pathogenesis of Down syndrome, one of the most prevalent human birth defects. The expression of this gene is analyzed in mouse embryos that are trisomic in chromosome 16 and are considered to be an animal model for Down syndrome. RNA blot-hybridization analysis and detailed analysis of HMG-14 protein levels indicate that mouse trisomy 16 embryos have approximately 1.5 times more HMG-14 mRNA and protein than their normal littermates, suggesting a direct gene dosage effect. The HMG-14 gene may be an additional marker for the Down syndrome. Chromosomal protein HMG-14 is a nucleosomal binding protein that may confer distinct properties to the chromatin structure of transcriptionally active genes and therefore may be a contributing factor in the etiology of the syndrome.

  19. Conserved gene arrangement in the origin region of the Streptomyces coelicolor chromosome.

    OpenAIRE

    1992-01-01

    A 23-kb fragment of the Streptomyces coelicolor chromosome spanning the dnaA region has been isolated as a cosmid clone. Nucleotide sequence analysis of a 5-kb portion shows that the genes for the RNase P protein (rnpA), ribosomal protein L34 (rpmH), the replication initiator protein (dnaA), and the beta subunit of DNA polymerase III (dnaN) are present in the highly conserved gene arrangement found in all eubacterial genomes studied so far. The dnaA-dnaN intergenic region is approximately 1 k...

  20. Cytokinesis breaks dicentric chromosomes preferentially at pericentromeric regions and telomere fusions.

    Science.gov (United States)

    Lopez, Virginia; Barinova, Natalja; Onishi, Masayuki; Pobiega, Sabrina; Pringle, John R; Dubrana, Karine; Marcand, Stéphane

    2015-02-01

    Dicentric chromosomes are unstable products of erroneous DNA repair events that can lead to further genome rearrangements and extended gene copy number variations. During mitosis, they form anaphase bridges, resulting in chromosome breakage by an unknown mechanism. In budding yeast, dicentrics generated by telomere fusion break at the fusion, a process that restores the parental karyotype and protects cells from rare accidental telomere fusion. Here, we observed that dicentrics lacking telomere fusion preferentially break within a 25- to 30-kb-long region next to the centromeres. In all cases, dicentric breakage requires anaphase exit, ruling out stretching by the elongated mitotic spindle as the cause of breakage. Instead, breakage requires cytokinesis. In the presence of dicentrics, the cytokinetic septa pinch the nucleus, suggesting that dicentrics are severed after actomyosin ring contraction. At this time, centromeres and spindle pole bodies relocate to the bud neck, explaining how cytokinesis can sever dicentrics near centromeres.

  1. Genetic linkage of mild pseudoachondroplasia (PSACH) to markers in the pericentromeric region of chromosome 19

    Energy Technology Data Exchange (ETDEWEB)

    Briggs, M.D.; Rasmussen, M.; Garber, P.; Rimoin, D.L.; Cohn, D.H. (Steven Spielberg Pediatric Research Center, Los Angeles, CA (United States)); Weber, J.L. (Marshfield Medical Research Foundation, WI (United States)); Yuen, J.; Reinker, K. (Univ. of Hawaii, Honolulu, HI (United States))

    1993-12-01

    Pseudoachondroplasia (PSACH) is a dominantly inherited form of short-limb dwarfism characterized by dysplastic changes in the spine, epiphyses, and metaphyses and early onset osteoarthropathy. Chondrocytes from affected individuals accumulate an unusual appearing material in the rough endoplasmic reticulum, which has led to the hypothesis that a structural abnormality in a cartilage-specific protein produces the phenotype. The authors recently identified a large family with a mild form of pseudoachondroplasia. By genetic linkage to a dinucleotide repeat polymorphic marker (D19S199), they have localized the disease gene to chromosome 19 (maximum lod score of 7.09 at a recombination fraction of 0.03). Analysis of additional markers and recombinations between the linked markers and the phenotype suggests that the disease gene resides within a 6.3-cM interval in the immediate pericentromeric region of the chromosome. 39 refs., 2 figs., 1 tab.

  2. Patterns of association in the human metaphase complement: ring analysis and estimation of associativity of specific chromosome regions.

    Science.gov (United States)

    Rodman, T C; Flehinger, B J; Squire, R D

    1978-02-23

    The pattern of metaphase chromosome association in the human complement was studied by two methods of statistical analysis of interchromosomal distances. Those methods included ring analysis in which a characteristic position of the centromere of each chromosome relative to the center of a two dimensional representation of a metaphase complement was defined, and estimation of the capacity for associativity of each of three regions of each chromosome: the centromere (c) and the ends of each arm (p, q). The following information was obtained: 1. In general, the distance from the center is directly related to chromosome size. 2. The most notable deviation from that size-related progression is displayed by the X chromosomes. The markedly peripheral position of the X is characteristic of both X's of the female and the single X of the male. 3. The relative associativity of each chromosome of the complement is, in general, inversely related to size with an additional preferential capacity of associativity displayed by the acrocentric chromosomes. Analyses of the different inter-regional classes established that the supplementary associativity factor of the acrocentric chromosomes was inherent in their pericentromeric and p-arm regions and excluded the ends of the q arms from participation in that factor. 4. Those analyses demonstrated that the specific morphology or 'geometry' of the acrocentric chromosomes contributes little to their high relative associativity. In addition to the tendency for the c/p regions of the acrocentric chromosomes to associate with each other, presumably because of their common function in nucleolar organization, those regions also displayed a propensity to associate with the distal regions of the arms of other chromosomes. A molecular basis for that propensity other than that of ribosomal DNA is postulated to be that of other fractions of highly reiterated DNA sequences. 5. Analysis of the relative associativities of each of the three regions

  3. Identification of the Sex-Determining Region of the Ceratitis Capitata Y Chromosome by Deletion Mapping

    Science.gov (United States)

    Willhoeft, U.; Franz, G.

    1996-01-01

    In the medfly Ceratitis capitata, the Y chromosome is responsible for determining the male sex. We have mapped the region containing the relevant factor through the analysis of Y-autosome translocations using fluorescence in situ hybridization with two different probes. One probe, the clone pY114, contains repetitive, Y-specific DNA sequences from C. capitata, while the second clone, pDh2-H8, consists of ribosomal DNA sequences from Drosophila hydei. Clone pY114 labeled most of the long arm and pDh2-H8 hybridizes to the short arm and the centromeric region of the long arm. In 12 of the analyzed 19 Y-autosome translocation strains, adjacent-1 segregation products survive to the late pupal or even adult stage and can, therefore, be sexed. This was correlated with the length of the Y fragment still present in these aberrant individuals and allowed us to map the male-determining factor to a region of the long arm representing ~15% of the entire Y chromosome. No additional factors, affecting for example fertility, were detected outside the male-determining region. PMID:8889534

  4. Nonsense Mutations in SMPX, Encoding a Protein Responsive to Physical Force, Result in X-Chromosomal Hearing Loss

    Science.gov (United States)

    Huebner, Antje K.; Gandia, Marta; Frommolt, Peter; Maak, Anika; Wicklein, Eva M.; Thiele, Holger; Altmüller, Janine; Wagner, Florian; Viñuela, Antonio; Aguirre, Luis A.; Moreno, Felipe; Maier, Hannes; Rau, Isabella; Gießelmann, Sebastian; Nürnberg, Gudrun; Gal, Andreas; Nürnberg, Peter; Hübner, Christian A.; del Castillo, Ignacio; Kurth, Ingo

    2011-01-01

    The fact that hereditary hearing loss is the most common sensory disorder in humans is reflected by, among other things, an extraordinary allelic and nonallelic genetic heterogeneity. X-chromosomal hearing impairment represents only a minor fraction of all cases. In a study of a Spanish family the locus for one of the X-chromosomal forms was assigned to Xp22 (DFNX4). We mapped the disease locus in the same chromosomal region in a large German pedigree with X-chromosomal nonsyndromic hearing impairment by using genome-wide linkage analysis. Males presented with postlingual hearing loss and onset at ages 3–7, whereas onset in female carriers was in the second to third decades. Targeted DNA capture with high-throughput sequencing detected a nonsense mutation in the small muscle protein, X-linked (SMPX) of affected individuals. We identified another nonsense mutation in SMPX in patients from the Spanish family who were previously analyzed to map DFNX4. SMPX encodes an 88 amino acid, cytoskeleton-associated protein that is responsive to mechanical stress. The presence of Smpx in hair cells and supporting cells of the murine cochlea indicates its role in the inner ear. The nonsense mutations detected in the two families suggest a loss-of-function mechanism underlying this form of hearing impairment. Results obtained after heterologous overexpression of SMPX proteins were compatible with this assumption. Because responsivity to physical force is a characteristic feature of the protein, we propose that long-term maintenance of mechanically stressed inner-ear cells critically depends on SMPX function. PMID:21549336

  5. Dynamics of rye chromosome 1R regions with high or low crossover frequency in homology search and synapsis development.

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    Nohelia T Valenzuela

    Full Text Available In many organisms, homologous pairing and synapsis depend on the meiotic recombination machinery that repairs double-strand DNA breaks (DSBs produced at the onset of meiosis. The culmination of recombination via crossover gives rise to chiasmata, which locate distally in many plant species such as rye, Secale cereale. Although, synapsis initiates close to the chromosome ends, a direct effect of regions with high crossover frequency on partner identification and synapsis initiation has not been demonstrated. Here, we analyze the dynamics of distal and proximal regions of a rye chromosome introgressed into wheat to define their role on meiotic homology search and synapsis. We have used lines with a pair of two-armed chromosome 1R of rye, or a pair of telocentrics of its long arm (1RL, which were homozygous for the standard 1RL structure, homozygous for an inversion of 1RL that changes chiasma location from distal to proximal, or heterozygous for the inversion. Physical mapping of recombination produced in the ditelocentric heterozygote (1RL/1RL(inv showed that 70% of crossovers in the arm were confined to a terminal segment representing 10% of the 1RL length. The dynamics of the arms 1RL and 1RL(inv during zygotene demonstrates that crossover-rich regions are more active in recognizing the homologous partner and developing synapsis than crossover-poor regions. When the crossover-rich regions are positioned in the vicinity of chromosome ends, their association is facilitated by telomere clustering; when they are positioned centrally in one of the two-armed chromosomes and distally in the homolog, their association is probably derived from chromosome elongation. On the other hand, chromosome movements that disassemble the bouquet may facilitate chromosome pairing correction by dissolution of improper chromosome associations. Taken together, these data support that repair of DSBs via crossover is essential in both the search of the homologous partner

  6. Early vertebrate chromosome duplications and the evolution of the neuropeptide Y receptor gene regions

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    Brenner Sydney

    2008-06-01

    Full Text Available Abstract Background One of the many gene families that expanded in early vertebrate evolution is the neuropeptide (NPY receptor family of G-protein coupled receptors. Earlier work by our lab suggested that several of the NPY receptor genes found in extant vertebrates resulted from two genome duplications before the origin of jawed vertebrates (gnathostomes and one additional genome duplication in the actinopterygian lineage, based on their location on chromosomes sharing several gene families. In this study we have investigated, in five vertebrate genomes, 45 gene families with members close to the NPY receptor genes in the compact genomes of the teleost fishes Tetraodon nigroviridis and Takifugu rubripes. These correspond to Homo sapiens chromosomes 4, 5, 8 and 10. Results Chromosome regions with conserved synteny were identified and confirmed by phylogenetic analyses in H. sapiens, M. musculus, D. rerio, T. rubripes and T. nigroviridis. 26 gene families, including the NPY receptor genes, (plus 3 described recently by other labs showed a tree topology consistent with duplications in early vertebrate evolution and in the actinopterygian lineage, thereby supporting expansion through block duplications. Eight gene families had complications that precluded analysis (such as short sequence length or variable number of repeated domains and another eight families did not support block duplications (because the paralogs in these families seem to have originated in another time window than the proposed genome duplication events. RT-PCR carried out with several tissues in T. rubripes revealed that all five NPY receptors were expressed in the brain and subtypes Y2, Y4 and Y8 were also expressed in peripheral organs. Conclusion We conclude that the phylogenetic analyses and chromosomal locations of these gene families support duplications of large blocks of genes or even entire chromosomes. Thus, these results are consistent with two early vertebrate

  7. A distinct type of heterochromatin at the telomeric region of the Drosophila melanogaster Y chromosome.

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    Sidney H Wang

    Full Text Available Heterochromatin assembly and its associated phenotype, position effect variegation (PEV, provide an informative system to study chromatin structure and genome packaging. In the fruit fly Drosophila melanogaster, the Y chromosome is entirely heterochromatic in all cell types except the male germline; as such, Y chromosome dosage is a potent modifier of PEV. However, neither Y heterochromatin composition, nor its assembly, has been carefully studied. Here, we report the mapping and characterization of eight reporter lines that show male-specific PEV. In all eight cases, the reporter insertion sites lie in the telomeric transposon array (HeT-A and TART-B2 homologous repeats of the Y chromosome short arm (Ys. Investigations of the impact on the PEV phenotype of mutations in known heterochromatin proteins (i.e., modifiers of PEV show that this Ys telomeric region is a unique heterochromatin domain: it displays sensitivity to mutations in HP1a, EGG and SU(VAR3-9, but no sensitivity to Su(z2 mutations. It appears that the endo-siRNA pathway plays a major targeting role for this domain. Interestingly, an ectopic copy of 1360 is sufficient to induce a piRNA targeting mechanism to further enhance silencing of a reporter cytologically localized to the Ys telomere. These results demonstrate the diversity of heterochromatin domains, and the corresponding variation in potential targeting mechanisms.

  8. A defined terminal region of the E. coli chromosome shows late segregation and high FtsK activity.

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    Marie Deghorain

    Full Text Available BACKGROUND: The FtsK DNA-translocase controls the last steps of chromosome segregation in E. coli. It translocates sister chromosomes using the KOPS DNA motifs to orient its activity, and controls the resolution of dimeric forms of sister chromosomes by XerCD-mediated recombination at the dif site and their decatenation by TopoIV. METHODOLOGY: We have used XerCD/dif recombination as a genetic trap to probe the interaction of FtsK with loci located in different regions of the chromosome. This assay revealed that the activity of FtsK is restricted to a ∼400 kb terminal region of the chromosome around the natural position of the dif site. Preferential interaction with this region required the tethering of FtsK to the division septum via its N-terminal domain as well as its translocation activity. However, the KOPS-recognition activity of FtsK was not required. Displacement of replication termination outside the FtsK high activity region had no effect on FtsK activity and deletion of a part of this region was not compensated by its extension to neighbouring regions. By observing the fate of fluorescent-tagged loci of the ter region, we found that segregation of the FtsK high activity region is delayed compared to that of its adjacent regions. SIGNIFICANCE: Our results show that a restricted terminal region of the chromosome is specifically dedicated to the last steps of chromosome segregation and to their coupling with cell division by FtsK.

  9. Nerve growth factor receptor gene is at human chromosome region 17q12-17q22, distal to the chromosome 17 breakpoint in acute leukemias

    Energy Technology Data Exchange (ETDEWEB)

    Huebner, K.; Isobe, M.; Chao, M.; Bothwell, M.; Ross, A.H.; Finan, J.; Hoxie, J.A.; Sehgal, A.; Buck, C.R.; Lanahan, A.

    1986-03-01

    Genomic and cDNA clones for the human nerve growth factor receptor have been used in conjunction with somatic cell hybrid analysis and in situ hybridization to localize the nerve growth factor receptor locus to human chromosome region 17q12-q22. Additionally, part, if not all, of the nerve growth factor receptor locus is present on the translocated portion of 17q (17q21-qter) from a poorly differential acute leukemia in which the chromosome 17 breakpoint was indistinguishable cytogenetically from the 17 breakpoint observed in the t(15;17)(q22;q21) translocation associated with acute promyelocytic leukemia. Thus the nerve growth factor receptor locus may be closely distal to the acute promyelocytic leukemia-associated chromosome 17 breakpoint at 17q21.

  10. Methods of Reprogramming to Induced Pluripotent Stem Cell Associated with Chromosomal Integrity and Delineation of a Chromosome 5q Candidate Region for Growth Advantage.

    Science.gov (United States)

    Sobol, Maria; Raykova, Doroteya; Cavelier, Lucia; Khalfallah, Ayda; Schuster, Jens; Dahl, Niklas

    2015-09-01

    Induced pluripotent stem cells (iPSCs) have brought great promises for disease modeling and cell-based therapies. One concern related to the use of reprogrammed somatic cells is the loss of genomic integrity and chromosome stability, a hallmark for cancer and many other human disorders. We investigated 16 human iPSC lines reprogrammed by nonintegrative Sendai virus (SeV) and another 16 iPSC lines generated by integrative lentivirus for genetic changes. At early passages we detected cytogenetic rearrangements in 44% (7/16) of iPSC lines generated by lentiviral integration whereas the corresponding figure was 6% (1/16) using SeV-based delivery. The rearrangements were numerical and/or structural with chromosomes 5 and 12 as the most frequently involved chromosomes. Three iPSC lines with chromosome 5 aberrations were derived from one and the same donor. We present in this study the aberrant karyotypes including a duplication of chromosome 5q13q33 that restricts a candidate region for growth advantage. Our results suggest that the use of integrative lentivirus confers a higher risk for cytogenetic abnormalities at early passages when compared to SeV-based reprogramming. In combination, our findings expand the knowledge on acquired cytogenetic aberrations in iPSC after reprogramming and during culture.

  11. Involvement of regions of the 4th and 7th chromosomes in the open-field activity of mice.

    Science.gov (United States)

    Clément, Y; Martin, B; Venault, P; Chapouthier, G

    1995-09-01

    Reactivity to a new environment was studied in mice, using an open-field procedure in two strains, C57BL/6By and ABP/Le, the F1 populations and the intercrosses F2 and backcross segregating populations. The analysis of the behavioral traits: peripheral and central activities, leaning, rearing and defecation in the parental strains made it possible to show that the ABP/Le strain was more reactive than C57BL/6By. In addition, the study of segregating, for four phenotypic markers, in F2 and backcross populations strongly suggested that two autosomal regions were involved in the control of open-field behavior: one in chromosomal region comprising the b locus on chromosome 4 and one in chromosomal region comprising the p locus on chromosome 7.

  12. Antibodies to left-handed Z-DNA bind to interband regions of Drosophila polytene chromosomes

    Science.gov (United States)

    Nordheim, Alfred; Pardue, Mary Lou; Lafer, Eileen M.; Möller, Achim; Stollar, B. David; Rich, Alexander

    1981-12-01

    Antibodies which are specific to the Z-DNA conformation have been purified and characterized on the basis of their binding to three different DNA polymers which can form this left-handed helix. These antibodies bind specifically to polytene chromosomes of Drosophila melanogaster as visualized by fluorescent staining. The staining is found in the interband regions and its intensity varies among different interbands in a reproducible manner. This is the first identification of the Z-DNA conformation in material of biological origin.

  13. Cloning and characterization of a putative human holocytochrome c-type synthetase gene (HCCS) isolated from the critical region for microphthalmia with linear skin defects (MLS)

    Energy Technology Data Exchange (ETDEWEB)

    Schaefer, L.; Ballabio, A.; Zoghbi, H.Y. [Baylor College of Medicine, Houston, TX (United States)

    1996-06-01

    Microphthalmia with linear skin defects syndrome (MLS) is an X-linked male-lethal disorder associated with X chromosomal rearrangements resulting in monosomy from Xpter to Xp22. Features include microphthalmia, sclerocornea, linear skin defects, and agenesis of the corpus callosum. Using a cross-species conservation strategy, an expressed sequence from the 450- to the 550-kb MLS critical region on Xp22 was identified by screening a human embryo cDNA library. Northern analysis revealed a transcript of {approx}2.6 kb in all tissues examined, with weaker expression of {approx}1.2- and {approx}5.2-kb transcripts. The strongest expression was observed in heart and skeletal muscle. Sequence analysis of a 3-kb cDNA contig revealed an 807-bp open reading frame encoding a putative 268-amino-acid-protein. Comparison of the sequence with sequences in the databases revealed homology with holocytochrome c-type synthetases, which catalyze the covalent addition of a heme group onto c-type cytochromes in the mitochondria. The c-type cytochromes are required for proper functioning of the electron transport pathway. The human gene (HGMW-approved symbol HCCS) and the corresponding murine gene characterized in this paper are the first mammalian holocytochrome c-type synthetases to be described in the literature. Because of the lack of a neuromuscular phenotype in MLS, it is uncertain whether the deletion of a mitochondrial holocytochrome synthetase would contribute to the phenotype seen in MLS. The expression pattern of this gene and knowledge about the function of holocytochrome synthetases, however, suggest that it is a good candidate for X-linked encephalomyopathies typically associated with mitochondrial dysfunction. 25 refs., 4 figs.

  14. Genomic study of the critical region of chromosome 21 associated to Down syndrome

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    Julio César Montoya

    2011-03-01

    Full Text Available Introduction: Previous reports have identified a region of chromosome 21 known as Down ayndrome critical region (DSCR in which the expression of some genes would modulate the main clinical characteristics of this pathology. In this sense, there is currently limited information on the architecture of the DSCR associated.Objective: To obtain in silico a detailed vision of the chromatin structure associated with the evaluation of genomic covariables contained in public data bases.Methods: Taking as reference the information consigned in the National Center for Biotechnology Information, the Genome Browser from the University of California at Santa Cruz and from the HapMap project, a chromosome walk along 21 Mb of the distal portion of chromosome 21q arm was performed. In this distal portion, the number of single nucleotide polymorphisms (SNP, number of CpG islands, repetitive elements, recombination frequencies, and topographical state of that chromatin were recorded.Results: The frequency of CpG islands and Ref genes increased in the more distal 1.2 Mb DSCR that contrast with those localized near to the centromere. The highest level of recombination calculated for women was registered in the 21q22.12 to 22.3 bands. DSCR 6 and 9 genes showed a high percentage of methylation in CpG islands in DNA from normal and trisomic fibroblasts. The DSCR2 gene exhibited high levels of open chromatin and also methylation in some lysine residues of the histone H3 as relevant characteristics.Conclusion: The existence of a genomic environment characterized by high values of recombination frequencies and CpG methylation in DSCR 6 and 9 and also DSCR2 genes led us to postulate that in non-disjunction detected in Down syndrome, complex genomic, epigenetic and environmental relationships regulate some processes of meiosis.

  15. Genomic study of the critical region of chromosome 21 associated to Down syndrome

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    Julio César Montoya

    2011-04-01

    Full Text Available Introduction: Previous reports have identified a region of chromosome 21 known as Down ayndrome critical region (DSCR in which the expression of some genes would modulate the main clinical characteristics of this pathology. In this sense, there is currently limited information on the architecture of the DSCR associated. Objective: To obtain in silico a detailed vision of the chromatin structure associated with the evaluation of genomic covariables contained in public data bases. Methods: Taking as reference the information consigned in the National Center for Biotechnology Information, the Genome Browser from the University of California at Santa Cruz and from the HapMap project, a chromosome walk along 21 Mb of the distal portion of chromosome 21q arm was performed. In this distal portion, the number of single nucleotide polymorphisms (SNP, number of CpG islands, repetitive elements, recombination frequencies, and topographical state of that chromatin were recorded. Results: The frequency of CpG islands and Ref genes increased in the more distal 1.2 Mb DSCR that contrast with those localized near to the centromere. The highest level of recombination calculated for women was registered in the 21q22.12 to 22.3 bands. DSCR 6 and 9 genes showed a high percentage of methylation in CpG islands in DNA from normal and trisomic fibroblasts. The DSCR2 gene exhibited high levels of open chromatin and also methylation in some lysine residues of the histone H3 as relevant characteristics. Conclusion: The existence of a genomic environment characterized by high values of recombination frequencies and CpG methylation in DSCR 6 and 9 and also DSCR2 genes led us to postulate that in non-disjunction detected in Down syndrome, complex genomic, epigenetic and environmental relationships regulate some processes of meiosis.

  16. Major chromosomal breakpoint intervals in breast cancer tumors co-localize with differentially methylated regions.

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    Man-Hung Eric eTang

    2012-12-01

    Full Text Available Solid tumors exhibit chromosomal rearrangements resulting in gain or loss of multiple loci (copy number variation and translocations that occasionally result in the creation of novel chimeric genes. In the case of breast cancer, although most individual tumors each have unique CNV landscape the breakpoints, as measured over large datasets, appear to be non-randomly distributed in the genome. Breakpoints show a significant regional concentration at genomic loci spanning perhaps several megabases. The proximal cause of these breakpoint concentrations is a subject of speculation but is, as yet, largely unknown. To shed light on this issue, we have performed a bio-statistical analysis on our previously published data for a set of 119 breast tumors and normal controls, where each sample has both high resolution CNV and methylation data. The method examined the distribution of closeness of breakpoint regions with differentially methylated regions, coupled with additional genomic parameters, such as repeat elements and designated fragile sites in the reference genome. Through this analysis, we have identified a set of 91 regional loci called breakpoint enriched differentially methylated regions (BEDMRs characterized by altered DNA methylation in cancer compared to normal cells that are associated with frequent breakpoint concentrations within a distance of 1Mb. BEDMR loci are further associated with local hypomethylation (66% concentrations of the Alu SINE repeats within 3Mb and tend to occur near a number of cancer related genes such as the protocadherins, AKT1, DUB3, GAB2. BEDMRs seem to deregulate members of the histone gene family and chromatin remodeling factors e.g JMJD1B which might affect the chromatin structure and disrupt coordinate signaling and repair. From this analysis we propose that preference for chromosomal breakpoints is related to genome structure coupled with alterations in DNA methylation and hence chromatin structure associated

  17. High-resolution recombination patterns in a region of human chromosome 21 measured by sperm typing.

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    Irene Tiemann-Boege

    2006-05-01

    Full Text Available For decades, classical crossover studies and linkage disequilibrium (LD analysis of genomic regions suggested that human meiotic crossovers may not be randomly distributed along chromosomes but are focused instead in "hot spots." Recent sperm typing studies provided data at very high resolution and accuracy that defined the physical limits of a number of hot spots. The data were also used to test whether patterns of LD can predict hot spot locations. These sperm typing studies focused on several small regions of the genome already known or suspected of containing a hot spot based on the presence of LD breakdown or previous experimental evidence of hot spot activity. Comparable data on target regions not specifically chosen using these two criteria is lacking but is needed to make an unbiased test of whether LD data alone can accurately predict active hot spots. We used sperm typing to estimate recombination in 17 almost contiguous ~5 kb intervals spanning 103 kb of human Chromosome 21. We found two intervals that contained new hot spots. The comparison of our data with recombination rates predicted by statistical analyses of LD showed that, overall, the two datasets corresponded well, except for one predicted hot spot that showed little crossing over. This study doubles the experimental data on recombination in men at the highest resolution and accuracy and supports the emerging genome-wide picture that recombination is localized in small regions separated by cold areas. Detailed study of one of the new hot spots revealed a sperm donor with a decrease in recombination intensity at the canonical recombination site but an increase in crossover activity nearby. This unique finding suggests that the position and intensity of hot spots may evolve by means of a concerted mechanism that maintains the overall recombination intensity in the region.

  18. Genome-wide association study identified a narrow chromosome 1 region associated with chicken growth traits.

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    Liang Xie

    Full Text Available Chicken growth traits are important economic traits in broilers. A large number of studies are available on finding genetic factors affecting chicken growth. However, most of these studies identified chromosome regions containing putative quantitative trait loci and finding causal mutations is still a challenge. In this genome-wide association study (GWAS, we identified a narrow 1.5 Mb region (173.5-175 Mb of chicken (Gallus gallus chromosome (GGA 1 to be strongly associated with chicken growth using 47,678 SNPs and 489 F2 chickens. The growth traits included aggregate body weight (BW at 0-90 d of age measured weekly, biweekly average daily gains (ADG derived from weekly body weight, and breast muscle weight (BMW, leg muscle weight (LMW and wing weight (WW at 90 d of age. Five SNPs in the 1.5 Mb KPNA3-FOXO1A region at GGA1 had the highest significant effects for all growth traits in this study, including a SNP at 8.9 Kb upstream of FOXO1A for BW at 22-48 d and 70 d, a SNP at 1.9 Kb downstream of FOXO1A for WW, a SNP at 20.9 Kb downstream of ENSGALG00000022732 for ADG at 29-42 d, a SNP in INTS6 for BW at 90 d, and a SNP in KPNA3 for BMW and LMW. The 1.5 Mb KPNA3-FOXO1A region contained two microRNA genes that could bind to messenger ribonucleic acid (mRNA of IGF1, FOXO1A and KPNA3. It was further indicated that the 1.5 Mb GGA1 region had the strongest effects on chicken growth during 22-42 d.

  19. Genomic Structure and Evolution of the Ancestral Chromosome Fusion Site in 2q13–2q14.1 and Paralogous Regions on Other Human Chromosomes

    Science.gov (United States)

    Fan, Yuxin; Linardopoulou, Elena; Friedman, Cynthia; Williams, Eleanor; Trask, Barbara J.

    2002-01-01

    Human chromosome 2 was formed by the head-to-head fusion of two ancestral chromosomes that remained separate in other primates. Sequences that once resided near the ends of the ancestral chromosomes are now interstitially located in 2q13–2q14.1. Portions of these sequences had duplicated to other locations prior to the fusion. Here we present analyses of the genomic structure and evolutionary history of >600 kb surrounding the fusion site and closely related sequences on other human chromosomes. Sequence blocks that closely flank the inverted arrays of degenerate telomere repeats marking the fusion site are duplicated at many, primarily subtelomeric, locations. In addition, large portions of a 168-kb centromere-proximal block are duplicated at 9pter, 9p11.2, and 9q13, with 98%–99% average sequence identity. A 67-kb block on the distal side of the fusion site is highly homologous to sequences at 22qter. A third ∼100-kb segment is 96% identical to a region in 2q11.2. By integrating data on the extent and similarity of these paralogous blocks, including the presence of phylogenetically informative repetitive elements, with observations of their chromosomal distribution in nonhuman primates, we infer the order of the duplications that led to their current arrangement. Several of these duplicated blocks may be associated with breakpoints of inversions that occurred during primate evolution and of recurrent chromosome rearrangements in humans. [Supplemental material is available online at http://www.genome.org. The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: T. Newman, C. Harris, and J. Young.] PMID:12421751

  20. Mapping a gene that determines erythrocytic GTP concentration to a region of mouse chromosome 9 which is syntenic to human chromosome 3p

    Energy Technology Data Exchange (ETDEWEB)

    Snyder, F.F.; Jenuth, J.P.; Noy, J.L. [Univ. of Calgary, Alberta (Canada)] [and others

    1994-09-01

    Inbred mouse strains were surveyed for erythrocytic GTP concentration by high performance liquid chromatography and found to fall into two groups. Strains having low GTP levels between 1.4-3.4 nmole/10{sup 9} cells are represented by C3H/HeJ. Strains having high GTP levels between 11.0 - 14.8 nmole/10{sup 9} cells are represented by C57BL/6J. Erythocytic ATP levels did not vary significantly among these strains (63-87 nmole/10{sup 9} cells). Crosses between low and high GTP strains gave F{sub 1} progeny having intermediate levels of GTP. The progeny of F{sub 1}`s backcrossed to paternal strains segregated in a 1:1 ratio for GTP concentration characteristic of the F{sub 1} and parental strain. We designated the GTP concentration-determining trait Gtpc. Typing of the twelve BXH recombinant inbred strains revealed 0/12 strain distribution pattern differences with Gtpc for loci on both chromosomes 5 and 9. Backcross analysis did not provide evidence for linkage of Gtpc to W (dominant white spotting) on chromosome 5 with 15/45 recombinants. Backcross analysis testing for linkage of Gtpc to transferrin (Trf) on chromosome 9 gave evidence for linkage with a recombination frequency of 9.68 {plus_minus} 3.07. DNA-based typing of repeat length polymorphic markers on chromosome 9 gave a map distance of 10.7 {plus_minus} 3.6 between D9 MITl4 and Gtpc and placed Gtpc on the telomeric side of Trf. This region of mouse chromosome 9 is syntenic to human chromosome 3p and encompasses a cluster of G-protein loci.

  1. Conserved gene arrangement in the origin region of the Streptomyces coelicolor chromosome.

    Science.gov (United States)

    Calcutt, M J; Schmidt, F J

    1992-01-01

    A 23-kb fragment of the Streptomyces coelicolor chromosome spanning the dnaA region has been isolated as a cosmid clone. Nucleotide sequence analysis of a 5-kb portion shows that the genes for the RNase P protein (rnpA), ribosomal protein L34 (rpmH), the replication initiator protein (dnaA), and the beta subunit of DNA polymerase III (dnaN) are present in the highly conserved gene arrangement found in all eubacterial genomes studied so far. The dnaA-dnaN intergenic region is approximately 1 kb and contains a cluster of at least 12 DnaA boxes with a consensus sequence of TTGTCCACA matching the consensus DnaA box in the phylogenetically related Micrococcus luteus. Two DnaA boxes precede the dnaA sequence. We propose that the chromosomal origin (oriC) of S. coelicolor lies between dnaA and dnaN. In related work, J. Zakrzewska-Czerwinska and H. Schrempf (J. Bacteriol. 174:2688-2693, 1992) have identified the homologous sequence from the closely-related Streptomyces lividans as capable of self-replication. PMID:1577691

  2. Chromosome region-specific libraries for human genome analysis. Final progress report, 1 March 1991--28 February 1994

    Energy Technology Data Exchange (ETDEWEB)

    Kao, F.T.

    1994-04-01

    The objectives of this grant proposal include (1) development of a chromosome microdissection and PCR-mediated microcloning technology, (2) application of this microtechnology to the construction of region-specific libraries for human genome analysis. During this grant period, the authors have successfully developed this microtechnology and have applied it to the construction of microdissection libraries for the following chromosome regions: a whole chromosome 21 (21E), 2 region-specific libraries for the long arm of chromosome 2, 2q35-q37 (2Q1) and 2q33-q35 (2Q2), and 4 region-specific libraries for the entire short arm of chromosome 2, 2p23-p25 (2P1), 2p21-p23 (2P2), 2p14-p16 (wP3) and 2p11-p13 (2P4). In addition, 20--40 unique sequence microclones have been isolated and characterized for genomic studies. These region-specific libraries and the single-copy microclones from the library have been used as valuable resources for (1) isolating microsatellite probes in linkage analysis to further refine the disease locus; (2) isolating corresponding clones with large inserts, e.g. YAC, BAC, P1, cosmid and phage, to facilitate construction of contigs for high resolution physical mapping; and (3) isolating region-specific cDNA clones for use as candidate genes. These libraries are being deposited in the American Type Culture Collection (ATCC) for general distribution.

  3. A gene for distal arthrogryposis Type I maps to the pericentromeric region of chromosome 9

    Energy Technology Data Exchange (ETDEWEB)

    Bamshad, M.; Watkins, W.S.; Zenger, R.K.; Bohnsack, J.F.; Carey, J.C.; Otterud, B.; Krakowiak, P.A.; Robertson, M.; Jorde, L.B. [Univ. of Utah Health Sciences Center, Salt Lake City, UT (United States)

    1994-12-01

    Club foot is one of the most common human congenital malformations. Distal arthrogryposis type I (DA-1) is a frequent cause of dominantly inherited club foot. Performing a genomewide search using short tandem repeat (STR) polymorphisms, we have mapped a DA-1 gene to the pericentromeric region of chromosome 9 in a large kindred. Linkage analysis has generated a positive lod score of 5.90 at {theta} = 0, with the marker GS-4. Multiple recombinants bracketing the region have been identified. Analysis of an additional family demonstrated no linkage to the same locus, indicating likely locus heterogeneity. Of the autosomal congenital contracture disorders causing positional foot deformities, this is the first to be mapped.

  4. Transcriptional organization of a 450-kb region of the human X chromosome in Xq28

    Energy Technology Data Exchange (ETDEWEB)

    Bione, S.; Tamanini, F.; Maestrini, E.; Tribioli, C.; Rivella, S.; Toniolo, D. (Instituto di Genetica Biochimica ed Evoluzionistica, Pavia (Italy)); Poustka, A. (German Cancer Research Center, Heidelberg (Germany))

    1993-11-15

    In this paper, the authors report the transcriptional organization of a 450-kb gene cluster in Xq28, flanked by the glucose-6-phosphate dehydrogenase and the color vision genes. CpG islands previously identified and mapped to distal Xq28 have helped in construction of a continuous contig of cosmids and in identification of cDNAs corresponding to eight transcripts. Thirteen to 16 small genes with CpG islands are clustered in a region of 250-300 kb. Many are highly expressed in muscle or brain and may be the genes responsible for muscle or neurological disorders mapped to distal Xq28. The analysis indicates that, in this region of the genome, genes not related in sequence are organized in transcriptional domains of 100 kb and that this organization may be important for establishing and regulating gene expression in relation to tissue distribution and X chromosome inactivation.

  5. Transcriptional organization of a 450-kb region of the human X chromosome in Xq28.

    Science.gov (United States)

    Bione, S; Tamanini, F; Maestrini, E; Tribioli, C; Poustka, A; Torri, G; Rivella, S; Toniolo, D

    1993-12-01

    In this paper, we report the transcriptional organization of a 450-kb gene cluster in Xq28, flanked by the glucose-6-phosphate dehydrogenase and the color vision genes. CpG islands previously identified and mapped to distal Xq28 have helped in construction of a continuous contig of cosmids and in identification of cDNAs corresponding to eight transcripts. Thirteen to 16 small genes with CpG islands are clustered in a region of 250-300 kb. Many are highly expressed in muscle or brain and may be the genes responsible for muscle or neurological disorders mapped to distal Xq28. Our analysis indicates that, in this region of the genome, genes not related in sequence are organized in transcriptional domains of 100 kb and that this organization may be important for establishing and regulating gene expression in relation to tissue distribution and X chromosome inactivation.

  6. Characterization of a gene from the EDM1-PSACH region of human chromosome 19p

    Energy Technology Data Exchange (ETDEWEB)

    Lennon, G.G.; Giorgi, D.; Martin, J.R. [Lawrence Livermore National Lab., CA (United States)] [and others

    1994-09-01

    Genetic linkage mapping has indicated that both multiple epiphyseal dysplasia (EDM1), a dominantly inherited chondrodysplasia, and pseudoachondroplasia (PSACH), a skeletal disorder associated with dwarfism, map to a 2-3 Mb region of human chromosome 19p. We have isolated a partial cDNA from this region using hybrid selection, and report on progress towards the characterization of the genomic structure and transcription of the corresponding gene. Sequence analysis of the cDNA to date indicates that this gene is likely to be expressed within extracellular matrix tissues. Defects in this gene or neighboring gene family members may therefore lead to EDM1, PSACH, or other connective tissue and skeletal disorders.

  7. NOR sites detected by Ag-dAPI staining of an unusual autosome chromosome of Bradysia hygida (Diptera:Sciaridae) colocalize with C-banded heterochromatic region.

    Science.gov (United States)

    Gaspar, Vanessa Pinatto; Borges, Alex Rodrigues; Fernandez, Maria Aparecida

    2002-01-01

    The study of chromosomes in insects is a good tool in mitotic process analysis, zoographic localization and evolution investigation. Among them, the Sciaridae offers a karyotype with a small number of chromosomes, where the heterochromatin and nucleolar organizer region, NOR, are easily analyzed in metaphase chromosomes obtained from cerebral ganglia squashes. In this work, the heterochromatic regions on Bradysia hygida mitotic chromosomes, revealed by C-banding, were identified as centromeric blocks on A and C chromosomes and as dark interstitial region in B and X chromosomes. By Ag-DAPI staining, active nucleolus organizer region, NOR, was revealed associated to the constitutive heterochromatin in the end of the C autosome chromosome. The C-band regions and the unusual ribosomal site localization are discussed.

  8. Physical map-based sizes of the centromeric regions of Arabidopsis thaliana chromosomes 1, 2, and 3.

    Science.gov (United States)

    Hosouchi, Tsutomu; Kumekawa, Norikazu; Tsuruoka, Hisano; Kotani, Hirokazu

    2002-08-31

    The sizes of the centromeric regions of Arabidopsis thaliana chromosomes 1, 2, and 3 were determined by construction of their physical maps on the basis of restriction analysis. As the reported centromeric regions contain large gaps in the middle due to highly repetitive sequences, appropriate probes for Southern hybridization were prepared from the sequences reported for the flanking regions and from the sequences of BAC and YAC clones newly isolated in this work, and restriction analysis was performed using DNA of a hypomethylated strain (ddm1). The sizes of the genetically defined centromeric regions were deduced to be 9 megabases (Mb), 4.2 Mb and 4.1 Mb, respectively (chromosome 1, from markers T22C23-t7 to T3P8-sp6; chromosome 2, from F5J15-sp6 to T15D9; chromosome 3, from T9G9-sp6 to T15M14; G. P. Copenhaver et al. Science, 286, 2468-2479, 1999). By combining the sizes of the centromeric regions previously estimated for chromosomes 4 and 5 and the sequence data reported for the A. thaliana genome, the total genome size of A. thaliana was estimated to be approximately 146.0 Mb.

  9. Characterization of FRA7B, a human common fragile site mapped at the 7p chromosome terminal region.

    Science.gov (United States)

    Bosco, Nazario; Pelliccia, Franca; Rocchi, Angela

    2010-10-01

    Common fragile sites (CFS) are specific regions of the mammalian chromosomes that are particularly prone to gaps and breaks. They are a cause of genome instability, and the location of many CFS correlates with breakpoints of aberrations recurrent in some cancers. The molecular characterization of some CFS has not clarified the causes of their fragility. In this work, by using fluorescence in situ hybridization analysis with BAC and PAC clones, we determined the DNA sequence of the CFS FRA7B. The FRA7B sequence was then analyzed to identify coding sequences and some structural features possibly involved in fragility. FRA7B spans about 12.2 megabases, and is therefore one of the largest CFS analyzed. It maps at the 7p21.3-22.3 chromosome bands, therefore at the interface of G- and R-band regions that are probably difficult to replicate. A 90-kilobase long sequence that presents very high flexibility values was identified at the very beginning of the more fragile CFS region. Three large genes (THSD7A, SDK1, and MAD1L1) and two miRNA genes (MIRN589 and MIRN339) map in the fragile region. The chromosome band 7p22 is a recurrent breakpoint in chromosome abnormalities in different types of neoplasm. FRA7B is the first characterized CFS located in a chromosome terminal region.

  10. A GENE FROM HUMAN-CHROMOSOME REGION-3P21 WITH REDUCED EXPRESSION IN SMALL-CELL LUNG-CANCER

    NARCIS (Netherlands)

    CARRITT, B; KOK, K; van den Berg, Anke; OSINGA, J; PILZ, A; HOFSTRA, RMW; DAVIS, MB; VANDERVEEN, AY; RABBITTS, PH; GULATI, K; BUYS, CHCM

    1992-01-01

    A combination of cytogenetic and molecular studies has implicated the p21 region of human chromosome 3 as the probable site of a gene the loss of which contributes to the development of small cell lung cancer. We report here the isolation of a gene from this region which is expressed in normal lung

  11. PCR-based panel for regional localization of genes on chromosome 15

    Energy Technology Data Exchange (ETDEWEB)

    McDaniel, L.D.; Zhang, B.; Schultz, R.A. [Univ. of Texas Southwestern Medical Center, Dallas (United States)

    1994-09-01

    As the number of genes mapped to specific human chromosomes continues to increase, the feasibility of identifying the gene involved in a human genetic disease via a `candidate gene` approach will continue to improve. Although fluorescence in situ hybridization offers one approach to achieve refined mapping, results are dependent on the size of the probe used, which is not optimal for cDNAs or ESTs. In contrast, a PCR-based approach can achieve mapping for clones <100 bp in size. Through the use of a previously described deletion of chromosome 15 and the 15/17 translocation common to acute promyelocytic leukemia, we have assembled a small panel of somatic cell hybrids that can be used to assign probes to the regions 15p-q15, 15q15-q22, and 15q22-ter. Primers specific for unique cDNA sequences were used to amplify genomic DNA through the polymerase chain reaction. With this approach, we have assigned hexosaminidase A and aggrecan1 to 15q22-qter and leukocyte tyrosine kinase to 15q15-22.

  12. Further evidence for a relationship between the 5p15 chromosome region and the oculoauriculovertebral anomaly.

    Science.gov (United States)

    Ala-Mello, Sirpa; Siggberg, Linda; Knuutila, Sakari; von Koskull, Harriet; Taskinen, Mervi; Peippo, Maarit

    2008-10-01

    The oculoauriculovertebral anomaly (OAV) or Goldenhar syndrome is a malformation complex that has been described in several chromosomal rearrangements. Among them a deletion of the terminal 5p has recurred in seven previous patients. We wish to report on an additional such patient in order to reinforce the significance of this genomic region in the cause of at least a subgroup of OAV cases. Future studies, particularly in the OAV patients with a lateral facial cleft, might define one genetic background of the disorder. Our patient had a complex translocation chromosome 45,XX, inv(2) (q32q37)mat, dic(5;21) (p15.3;q22.3)dn, resulting in a terminal 5p deletion, a terminal deletion of 21q demonstrated by FISH studies, and a duplication of 21q22.11-q22.12 documented by molecular karyotyping. In addition to OAV she developed myelodysplasia treated with bone marrow transplantation. We discuss her clinical findings with reference to her karyotype findings and review the patients with OAV and a terminal deletion of 5p. Copyright 2008 Wiley-Liss, Inc.

  13. Hominoid chromosomal rearrangements on 17q map to complex regions of segmental duplication

    OpenAIRE

    Cardone, Maria Francesca; Jiang, Zhaoshi; D'Addabbo, Pietro; Archidiacono, Nicoletta; Rocchi, Mariano; Eichler, Evan E.; Ventura, Mario

    2008-01-01

    Background Chromosomal rearrangements, such as translocations and inversions, are recurrent phenomena during evolution, and both of them are involved in reproductive isolation and speciation. To better understand the molecular basis of chromosome rearrangements and their part in karyotype evolution, we have investigated the history of human chromosome 17 by comparative fluorescence in situ hybridization (FISH) and sequence analysis. Results Human bacterial artificial chromosome/p1 artificial ...

  14. Replication intermediate analysis confirms that chromosomal replication origin initiates from an unusual intergenic region in Caulobacter crescentus.

    Science.gov (United States)

    Brassinga, A K; Marczynski, G T

    2001-11-01

    The alpha-proteobacterium Caulobacter crescentus possesses a developmental cell cycle that restricts chromosome replication to a stalked cell type. The proposed C.crescentus chromosome replication origin (Cori) lies between hemE and RP001, an unusual intergenic region not previously associated with bacterial replication origins, although a similar genomic arrangement is also present at the putative replication origin in the related bacterium Rickettsia prowazekii. The cloned Cori supports autonomous plasmid replication selectively in the stalked cell type implying that replication of the entire chromosome also initiates between hemE and RP001. To confirm this location, we applied the 2-D (N/N) agarose gel electrophoresis technique to resolve and identify chromosome replication intermediates throughout a 30 kb region spanning Cori. Replication initiation in Cori was uniquely characterized by an 'origin bubble and Y-arc' pattern and this observation was supported by simple replication fork 'Y-arc' patterns that characterized the regions flanking Cori. These replication forks originated bi-directionally from within Cori as determined by the fork direction assay. Therefore, chromosomal replication initiates from the unusual hemE/RP001 intergenic region that we propose represents a new class of replication origins.

  15. A region of euchromatin coincides with an extensive tandem repeat on the mouse (Mus musculus) inactive X chromosome.

    Science.gov (United States)

    Darrow, Emily M; Seberg, Andrew P; Das, Sunny; Figueroa, Debbie M; Sun, Zhuo; Moseley, Shawn C; Chadwick, Brian P

    2014-09-01

    Euchromatic features are largely absent from the human inactive X chromosome (Xi), with the exception of several large tandem repeats that can be detected as euchromatin bands at metaphase. Despite residing megabases apart, these tandem repeats make frequent inactive X-specific interactions. The mouse homologue has been reported for at least one of the tandem repeats, but whether the mouse Xi is also characterized by distinct bands of euchromatin remains unknown. We examined the mouse Xi for the presence of euchromatin bands by examining the pattern of histone H3 dimethylated at lysine 4 and detected two major signals. The first band resides in the subtelomeric region of band XF5 and may correspond to the pseudoautosomal region. The second band localizes to XE3 and coincides with an extensive complex repeat composed of a large tandem and inverted repeat segment as well as several large short interspersed nuclear element (SINE)-rich tandem repeats. Fluorescence in situ hybridization reveals that sequences with homology to the repeat region are scattered along the length of the Y chromosome. Immunofluorescence analysis of histone H3 trimethylated at lysine 9 on metaphase chromosomes indicates that the repeat region corresponds to a band of constitutive heterochromatin on the male X and female active X chromosomes, whereas the euchromatin signal appears to be female specific. These data suggest that the band of euchromatin observed at XE3 is unique to the mouse Xi, comparable to the chromatin arrangement of several large tandem repeats located on the human X chromosome.

  16. Investigation of the chromosome regions with significant affinity for the nuclear envelope in fruit fly--a model based approach.

    Directory of Open Access Journals (Sweden)

    Nicholas Allen Kinney

    Full Text Available Three dimensional nuclear architecture is important for genome function, but is still poorly understood. In particular, little is known about the role of the "boundary conditions"--points of attachment between chromosomes and the nuclear envelope. We describe a method for modeling the 3D organization of the interphase nucleus, and its application to analysis of chromosome-nuclear envelope (Chr-NE attachments of polytene (giant chromosomes in Drosophila melanogaster salivary glands. The model represents chromosomes as self-avoiding polymer chains confined within the nucleus; parameters of the model are taken directly from experiment, no fitting parameters are introduced. Methods are developed to objectively quantify chromosome territories and intertwining, which are discussed in the context of corresponding experimental observations. In particular, a mathematically rigorous definition of a territory based on convex hull is proposed. The self-avoiding polymer model is used to re-analyze previous experimental data; the analysis suggests 33 additional Chr-NE attachments in addition to the 15 already explored Chr-NE attachments. Most of these new Chr-NE attachments correspond to intercalary heterochromatin--gene poor, dark staining, late replicating regions of the genome; however, three correspond to euchromatin--gene rich, light staining, early replicating regions of the genome. The analysis also suggests 5 regions of anti-contact, characterized by aversion for the NE, only two of these correspond to euchromatin. This composition of chromatin suggests that heterochromatin may not be necessary or sufficient for the formation of a Chr-NE attachment. To the extent that the proposed model represents reality, the confinement of the polytene chromosomes in a spherical nucleus alone does not favor the positioning of specific chromosome regions at the NE as seen in experiment; consequently, the 15 experimentally known Chr-NE attachment positions do not

  17. Localisation of the gene for achondroplasia to the telomeric region of chromosome 4p

    Energy Technology Data Exchange (ETDEWEB)

    Stoilov, I.; Velinov, M.; Kilpatrick, M.W. [and others

    1994-09-01

    Achondroplasia (ACH), the most common type of genetic dwarfism, is characterized by a variety of skeletal anomalies including disproportionate short stature and rhizomelic shortening of the extremities. The disorder is inherited as an autosomal dominant trait, with a prevalence of 1-15 per 100,000 live births. The etiology of ACH remains unknown, although evidence points to a defect in the maturation of the chondrocytes in the growth plate of the cartilage. To determine the location of the gene responsible for ACH, a panel of 14 families with a total of 43 meioses was genotyped for 40 polymorphic markers for loci randomly distributed throughout the genome. The first significant positive Lod score was obtained for the locus D4S127 (Zmax=3.65 at {theta}=0.03). A series of 20 markers for chromosome 4p16.3 loci were then used to determine the most likely position of the ACH gene. Two additional loci, D4S412 and IDUA, showed strong linkage to the disease (Zmax=3.34 at {theta}=0.03 and Zmax=3.35 at {theta}=0.0, respectively). Multipoint analysis and direct counting of recombinants places the ACH gene in a 2.5 cM region between the marker D4S43 and the chromosome 4p telomere. No evidence was found for genetic heterogeneity. The ACH region contains a number of genes, including that for the fibroblast growth factor receptor FGFR3, which are being evaluated as candidates for the ACH gene. This identification of tightly linked polymorphic markers, as well as being the first step in the characterization of the ACH gene, offers the possibility of DNA based prenatal diagnosis of this disorder.

  18. Forensic analysis of polymorphism and regional stratification of Y-chromosomal microsatellites in Belarus.

    Science.gov (United States)

    Rebała, Krzysztof; Tsybovsky, Iosif S; Bogacheva, Anna V; Kotova, Svetlana A; Mikulich, Alexei I; Szczerkowska, Zofia

    2011-01-01

    Nine loci defining minimal haplotypes and four other Y-chromosomal short tandem repeats (Y-STRs) DYS437, DYS438, DYS439 and GATA H4.1 were analysed in 414 unrelated males residing in four regions of Belarus. Haplotypes of 328 males were further extended by 7 additional Y-STRs: DYS388, DYS426, DYS448, DYS456, DYS458, DYS460 and DYS635. The 13-locus haplotype diversity was 0.9978 and discrimination capacity was 78.7%, indicating presence of identical haplotypes among unrelated males. Seven additional Y-STRs enabled almost complete discrimination of undifferentiated 13-locus haplotypes, increasing haplotype diversity to 0.9998 and discrimination capacity to 97.9%. Analysis of molecular variance of minimal haplotypes excluded the use of a Y-STR database for Belarusians residing in northeastern Poland as representative for the Belarusian population in forensic practice, and revealed regional stratification within the country. However, four additional markers (DYS437, DYS438, DYS439 and GATA H4.1) were shown to eliminate the observed geographical substructure among Belarusian males. The results imply that in case of minimal and PowerPlex Y haplotypes, a separate frequency database should be used for northern Belarus to estimate Y-STR profile frequencies in forensic casework. In case of Yfiler haplotypes, regional stratification within Belarus may be neglected.

  19. Deletion and duplication within the p11.2 region of chromosome 17

    Energy Technology Data Exchange (ETDEWEB)

    McCorquodale, D.J.; McCorquodale, M.; Bereziouk, O. [Univ. of Illinois College of Medicine, Chicago, IL (United States)] [and others

    1994-09-01

    A 7 1/2-year-old male patient presented with mild mental retardation, speech delay, hyperactivity, behavioral problems, mild facial hypoplasia, short broad hands, digital anomalies, and self-injurious behavior. Chromosomes obtained from peripheral blood cells revealed a deletion of 17p11.2 in about 40% of the metaphases examined, suggesting that the patient had Smith-Magenis Syndrome. A similar pattern of mosaicism in peripheral blood cells, but not in fibroblasts in which all cells displayed the deletion, has been previously reported. Since some cases of Smith-Magenis Syndrome have a deletion that extends into the region associated with Charcot-Marie-Tooth (CMT) Syndrome, we examined interphase cells with a CMT1A-specific probe by the method of fluorescence in situ hybridization. The CMT1A region was not deleted, but about 40% of the cells gave signals indicating a duplication of the CMT1A region. The patient has not presented neuropathies associated with CMT at this time. Future tracking of the patient should be informative.

  20. Sequence analysis of 21 genes located in the Kartagener syndrome linkage region on chromosome 15q.

    Science.gov (United States)

    Geremek, Maciej; Schoenmaker, Frederieke; Zietkiewicz, Ewa; Pogorzelski, Andrzej; Diehl, Scott; Wijmenga, Cisca; Witt, Michal

    2008-06-01

    Primary ciliary dyskinesia (PCD) is a rare genetic disorder, which shows extensive genetic heterogeneity and is mostly inherited in an autosomal recessive fashion. There are four genes with a proven pathogenetic role in PCD. DNAH5 and DNAI1 are involved in 28 and 10% of PCD cases, respectively, while two other genes, DNAH11 and TXNDC3, have been identified as causal in one PCD family each. We have previously identified a 3.5 cM (2.82 Mb) region on chromosome 15q linked to Kartagener syndrome (KS), a subtype of PCD characterized by the randomization of body organ positioning. We have now refined the KS candidate region to a 1.8 Mb segment containing 18 known genes. The coding regions of these genes and three neighboring genes were subjected to sequence analysis in seven KS probands, and we were able to identify 60 single nucleotide sequence variants, 35 of which resided in mRNA coding sequences. However, none of the variations alone could explain the occurrence of the disease in these patients.

  1. Partial hexasomy for the Prader-Willi-Angelman syndrome critical region due to a maternally inherited large supernumerary marker chromosome.

    Science.gov (United States)

    Hoppman-Chaney, Nicole L; Dawson, D Brian; Nguyen, Lai; Sengupta, Sunanda; Reynolds, Kara; McPherson, Elizabeth; Velagaleti, Gopalrao

    2010-08-01

    Extra copies of the Prader-Willi-Angelman syndrome critical region (PWASCR) have been shown to have detrimental phenotypic effects depending on the parent of origin. Hexasomy for the PWASCR is rare; only 6 cases have been described to date. We report on a 15-year-old girl referred for developmental delay and seizures with a mosaic tricentric small marker chromosome (SMC) 15 identified by routine G-banding chromosome studies. C-banding and FISH confirmed the presence of three chromosome 15 centromeres as well as four copies of the PWASCR on the SMC in approximately 60% of interphase cells. Microsatellite genotyping documented maternal inheritance of the SMC, and methylation-sensitive multiplex ligation-dependent PCR amplification (MS-MLPA) showed that the extra copies of the PWASCR contained on the marker chromosome bear a methylation pattern similar to a normal maternal chromosome, implying maternal inheritance. These findings are consistent with the patient's phenotype as paternal inheritance of such a marker chromosome is thought to be benign. However, this patient's phenotype is the mildest described to date and may be a result of mosaicism for the SMC.

  2. Genetic linkage studies in familial partial epilepsy: Exclusion of the human chromosome regions syntenic to the El-1 mouse locus

    Energy Technology Data Exchange (ETDEWEB)

    Lopes-Cendes, I. [Montreal General Hospital (Canada); Mulley, J.C. [Alelaide Children`s Hospital (Canada); Andermann, E. [Montreal Neurological Institute and Hospital, Quebec (Canada)] [and others

    1994-09-01

    Recently, six families with a familial form of partial epilepsy were described. All pedigrees showed autosomal dominant inheritance with incomplete penetrance. Affected individuals present with predominantly nocturnal seizures with frontal lobe semiology. In 1959, a genetic mouse model for partial epilepsy, the El mouse, was reported. In the El mouse, a major seizure susceptibility gene, El-1, segregates in an autosomal dominant fashion and has been localized to a region distal to the centromere of mouse chromosome 9. Comparative genetic maps between man and mouse have been used for prediction of localization of several human disease genes. Because the region of mouse chromosome 9 that is the most likely to contain the El-1 locus is syntenic to regions on human chromosomes 3q21-p22, 3q21-q23.3, 6q12 and 15q24, we adopted the candidate gene approach as an initial linkage strategy. Twenty-two polymorphic microsatellite markers covering these regions were used for genotyping individuals in the three larger families ascertained, two of which are Australian and one French-Canadian. Negative two-point lod scores were obtained separately for each family. The analysis of all three families combined significantly excludes the candidate regions on chromosomes 3, 6 and 15.

  3. Evaluation of single nucleotide polymorphisms in chromosomal regions impacting pregnancy status in cattle.

    Science.gov (United States)

    Psaros, K M; McDaneld, T G; Kuehn, L A; Snelling, W M; Keele, J W

    2015-03-01

    Reproductive success is an important component of commercial beef cattle production, and identification of DNA markers with predictive merit for reproductive success would facilitate accurate prediction of mean daughter pregnancy rate, enabling effective selection of bulls to improve female fertility. A previous study identified SNP associated with beef cattle reproductive efficiency based on a genomewide association analysis approach using genotyping multiple-animal pools of DNA to increase the number of animals that could be genotyped with available resources. For the current study, we expand on this previous study by individually genotyping cattle from the pooling study for 89 SNP that were associated with female pregnancy rate. The aims of the study were to confirm the results of the pooling study and, more specifically, identify modes of gene action and DNA variations such as haplotypes that would not be possible with pooled genotyping. Eighty-nine SNP selected from the pooling study were evaluated using the Sequenom MassARRAY system to individually genotype animals from populations evaluated in the pooling study, including both and breeds. From this research, regions on chromosomes 5 (26.3-48.1 Mb; UMD3.1 assembly) and 9 (37,436,575 bp; UMD3.1 assembly), first identified in the previous pooling study, were shown through individual genotyping to harbor genetic variation ( reproductive efficiency in interspecific crosses ( and ) of cattle. Each of these markers exhibited additive (vs. dominant) gene action. Additionally, a haplotype block harboring an allele of origin with negative effects on reproduction was identified on chromosome 5 in interspecific composite breeds of × composites.

  4. Idiopathic cases of male infertility from a region in India show low incidence of Y-chromosome microdeletion

    Indian Academy of Sciences (India)

    R Ambasudhan; K Singh; J K Agarwal; S K Singh; A Khanna; R K Sah; I Singh; R Raman

    2003-09-01

    Chromosomal and Y-chromosomal microdeletion analysis has been done in cases of idiopathic infertility with the objective of evaluating the frequency of chromosomal and molecular anomaly as the causal factor of infertility. Barring a few cases of Klinefelter syndrome (XXY or XY/XXY mosaics), no chromosomal anomaly was encountered. Y-microdeletion was analysed by PCR-screening of STSs from different regions of the AZF (AZFa, AZFb, AZFc) on the long arm of the Y, as well as by using DNA probes of the genes RBM, DAZ (Yq), DAZLA (an autosomal homologue of DAZ) and SRY (Yp; sex determining gene). Out of 177 cases examined, 9 (azoospermia – 8 and oligoasthenospermia – 1) showed partial deletion of AZF. The size of deletion varied among patients but AZFc was either totally or partially removed in all of them. In contrast, no deletion was detected in AZFa. Testis biopsy done on a limited number of cases (50) showed diverse stages of spermatogenic arrest with no specific correlation with the genotype. The frequency of Y-chromosome microdeletion in our samples (∼ 5%) is much lower than the frequency (∼ 10%) reported globally and the two previous reports from India. We contend that the frequency may be affected by population structures in different geographical regions.

  5. Homomorphic ZW chromosomes in a wild strawberry show distinctive recombination heterogeneity but a small sex-determining region.

    Science.gov (United States)

    Tennessen, Jacob A; Govindarajulu, Rajanikanth; Liston, Aaron; Ashman, Tia-Lynn

    2016-09-01

    Recombination in ancient, heteromorphic sex chromosomes is typically suppressed at the sex-determining region (SDR) and proportionally elevated in the pseudoautosomal region (PAR). However, little is known about recombination dynamics of young, homomorphic plant sex chromosomes. We examine male and female function in crosses and unrelated samples of the dioecious octoploid strawberry Fragaria chiloensis in order to map the small and recently evolved SDR controlling both traits and to examine recombination patterns on the incipient ZW chromosome. The SDR of this ZW system is located within a 280 kb window, in which the maternal recombination rate is lower than the paternal one. In contrast to the SDR, the maternal PAR recombination rate is much higher than the rates of the paternal PAR or autosomes, culminating in an elevated chromosome-wide rate. W-specific divergence is elevated within the SDR and a single polymorphism is observed in high species-wide linkage disequilibrium with sex. Selection for recombination suppression within the small SDR may be weak, but fluctuating sex ratios could favor elevated recombination in the PAR to remove deleterious mutations on the W. The recombination dynamics of this nascent sex chromosome with a modestly diverged SDR may be typical of other dioecious plants.

  6. On the Wegener granulomatosis associated region on chromosome 6p21.3

    Directory of Open Access Journals (Sweden)

    Csernok Elena

    2006-03-01

    Full Text Available Abstract Background Wegener granulomatosis (WG belongs to the heterogeneous group of systemic vasculitides. The multifactorial pathophysiology of WG is supposedly caused by yet unknown environmental influence(s on the basis of genetic predisposition. The presence of anti-neutrophil cytoplasmic antibodies (ANCA in the plasma of patients and genetic involvement of the human leukocyte antigen system reflect an autoimmune background of the disease. Strong associations were revealed with WG by markers located in the major histocompatibility complex class II (MHC II region in the vicinity of human leukocyte antigen (HLA-DPB1 and the retinoid X receptor B (RXRB loci. In order to define the involvement of the 6p21.3 region in WG in more detail this previous population-based association study was expanded here to the respective 3.6 megabase encompassing this region on chromosome 6. The RXRB gene was analysed as well as a splice-site variation of the butyrophilin-like (BTNL2 gene which is also located within the respective region. The latter polymorphism has been evaluated here as it appears as a HLA independent susceptibility factor in another granulomatous disorder, sarcoidosis. Methods 150–180 German WG patients and a corresponding cohort of healthy controls (n = 100–261 were used in a two-step study. A panel of 94 microsatellites was designed for the initial step using a DNA pooling approach. Markers with significantly differing allele frequencies between patient and control pools were individually genotyped. The RXRB gene was analysed for single strand conformation polymorphisms (SSCP and restriction fragment length polymorphisms (RFLP. The splice-site polymorphism in the BTNL2 gene was also investigated by RFLP analysis. Results A previously investigated microsatellite (#1.0.3.7, Santa Cruz genome browser (UCSC May 2004 Freeze localisation: chr6:31257596-34999883, which was used as a positive control, remained associated throughout the whole two

  7. A high-resolution map of the chromosomal region surrounding the nude gene

    Energy Technology Data Exchange (ETDEWEB)

    Blackburn, C.C.; Griffith, J.; Morahan, G. [Royal Melbourne Hospital, Victoria (Australia)

    1995-03-20

    The nude mutation produces the apparently disparate phenotypes of hairlessness and congenital thymic aplasia. These pleiotropic defects are the result of a single, autosomal recessive mutation that was previously mapped to a 9-cM region of murine chromosome 11 bounded by loci encoding the acetylcholine receptor P subunit and myeloperoxidase. In this study, exclusion mapping of a panel of congenic nude strains was used to place the nude locus between the microsatellite loci D11Nds1 and D11Mit8. The relative distance from nude to each of these loci was determined by analyzing a large segregating cross. Thus, nude lies 1.4 cM distal to D11Nds1 and is 0.5 cM proximal to D11Mit8. Mice that carried recombinational breakpoints between D11Nds1 and D11Mit8 were further analyzed at the loci Evi-2 and D11Mit34, which placed nu 0.2 cM proximal to these markers. D11Nds1 and Evi-2/D11Mit34 thus define the new proximal and distal boundaries, respectively, for the nu interval. We also report the typing of the above microsatellite markers in the AKXD, AKXL, BXD, CXB, and BXH recombinant inbred strains, which confirmed the relative order and separation of loci in this region. 47 refs., 3 figs., 1 tab.

  8. Disruption of Imprinted Genes at Chromosome Region 11p15.5 in Paediatric Rhabdomyosarcoma

    Directory of Open Access Journals (Sweden)

    John Anderson

    1999-10-01

    Full Text Available Rhabdomyosarcomas are characterized by loss of heterozygosity (LOH at chromosome region 11pl5.5, a region known to contain several imprinted genes including insulin-like growth factor 2 (IGF2, H19, p57KIP2. We analyzed 48 primary tumour samples and found distinct genetic changes at 11p15.5 in alveolar and embryonal histological subtypes. LOH was a feature of embryonal tumours, but at a lower frequency than previous studies. Loss of imprinting (LOI of the IGF2 gene was detected in 6 of 13 informative cases, all harbouring PAX3—FKHR or PAX7—FKHR fusion genes characteristic of alveolar histology. In contrast, H19 imprinting was maintained in 14 of 15 informative cases and the case with H19 LOI had maintenance of the IGF2 imprint indicating separate mechanisms controlling imprinting of IGF2 and H19. The adult promoter of IGF2, P1, was used in 5 of 14 tumours and its expression was unrelated to IGF2 imprinting status implying a further mechanism of altered IGF2 regulation. The putative tumour suppressor gene p57KIP2 was expressed in 15 of 29 tumours and expression was unrelated to allele status. Moreover, in tumours with p57KIP2 expression, there was no evidence for inactivating mutations, suggesting that p57KIP2 is not a tumour suppressor in rhabdomyosarcoma.

  9. Identification and characterization of genomic regions on chromosomes 4 and 8 that control the rate of photosynthesis in rice leaves

    Science.gov (United States)

    Adachi, Shunsuke; Tsuru, Yukiko; Nito, Naoko; Murata, Kazumasa; Yamamoto, Toshio; Ebitani, Takeshi; Ookawa, Taiichiro; Hirasawa, Tadashi

    2011-01-01

    DNA marker-assisted selection appears to be a promising strategy for improving rates of leaf photosynthesis in rice. The rate of leaf photosynthesis was significantly higher in a high-yielding indica variety, Habataki, than in the most popular Japanese variety, Koshihikari, at the full heading stage as a result of the higher level of leaf nitrogen at the same rate of application of nitrogen and the higher stomatal conductance even when the respective levels of leaf nitrogen were the same. The higher leaf nitrogen content of Habataki was caused by the greater accumulation of nitrogen by plants. The higher stomatal conductance of Habataki was caused by the higher hydraulic conductance. Using progeny populations and selected lines derived from a cross between Koshihikari and Habataki, it was possible to identify the genomic regions responsible for the rate of photosynthesis within a 2.1 Mb region between RM17459 and RM17552 and within a 1.2 Mb region between RM6999 and RM22529 on the long arm of chromosome 4 and on the short arm of chromosome 8, respectively. The designated region on chromosome 4 of Habataki was responsible for both the increase in the nitrogen content of leaves and hydraulic conductance in the plant by increasing the root surface area. The designated region on chromosome 8 of Habataki was responsible for the increase in hydraulic conductance by increasing the root hydraulic conductivity. The results suggest that it may be possible to improve photosynthesis in rice leaves by marker-assisted selection that focuses on these regions of chromosomes 4 and 8. PMID:21296764

  10. Identification and characterization of genomic regions on chromosomes 4 and 8 that control the rate of photosynthesis in rice leaves.

    Science.gov (United States)

    Adachi, Shunsuke; Tsuru, Yukiko; Nito, Naoko; Murata, Kazumasa; Yamamoto, Toshio; Ebitani, Takeshi; Ookawa, Taiichiro; Hirasawa, Tadashi

    2011-03-01

    DNA marker-assisted selection appears to be a promising strategy for improving rates of leaf photosynthesis in rice. The rate of leaf photosynthesis was significantly higher in a high-yielding indica variety, Habataki, than in the most popular Japanese variety, Koshihikari, at the full heading stage as a result of the higher level of leaf nitrogen at the same rate of application of nitrogen and the higher stomatal conductance even when the respective levels of leaf nitrogen were the same. The higher leaf nitrogen content of Habataki was caused by the greater accumulation of nitrogen by plants. The higher stomatal conductance of Habataki was caused by the higher hydraulic conductance. Using progeny populations and selected lines derived from a cross between Koshihikari and Habataki, it was possible to identify the genomic regions responsible for the rate of photosynthesis within a 2.1 Mb region between RM17459 and RM17552 and within a 1.2 Mb region between RM6999 and RM22529 on the long arm of chromosome 4 and on the short arm of chromosome 8, respectively. The designated region on chromosome 4 of Habataki was responsible for both the increase in the nitrogen content of leaves and hydraulic conductance in the plant by increasing the root surface area. The designated region on chromosome 8 of Habataki was responsible for the increase in hydraulic conductance by increasing the root hydraulic conductivity. The results suggest that it may be possible to improve photosynthesis in rice leaves by marker-assisted selection that focuses on these regions of chromosomes 4 and 8.

  11. Excess functional copy of allele at chromosomal region 11p15 may cause Wiedemann-Beckwith (EMG) syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kubota, T.; Saitoh, S.; Jinno, Y.; Niikawa, N.; Matsumoto, T. [Nagasaki Univ. School of Medicine (Japan); Narahara, K. [Okayama Univ. School of Medicine, Okayama (Japan); Fukushima, Y. [Saitama Children`s Hospital, Iwatsuki (Japan)

    1994-02-15

    Wiedemann-Beckwith syndrome (WBS) is a genetic disorder with overgrowth and predisposition to Wilms` tumor. The putative locus of the gene responsible for this syndrome is assigned to chromosome region 11p15.5, and genomic imprinting in this region has been proposed: the paternally derived gene(s) at 11p15.5 is selectively expressed, while the maternally transmitted gene(s) is inactive. The authors examined 18 patients for the parental origin of their 11p15 regions. DNA polymorphism analyses using 6 loci on chromosome 11 showed that 2 patients with duplications of 11p15 regions from their respective fathers and one from the mother, indicating the transmission of an excessive paternal gene at 11p15 to each patient. The result, together with the previous findings in karyotypically normal or abnormal patients and in overgrowth mouse experiments, are consistent with imprinting hypothesis that overexpression of paternally derived gene(s) at 11p15.5, probably the human insulin-like growth factor II (IFG-II) gene, may cause the phenotype. Total constitutional uniparental paternal disomy (UPD) or segmental UPD for the 6 loci examined of chromosome 11 was not observed in our 12 sporadic patients. In order to explain completely the inheritance of this syndrome in patients with various chromosomal constitutions, the authors propose an alternative imprinting mechanism involving the other locus that may be paternally imprinted and may suppress the expression of this gene. 28 refs., 3 figs., 1 tab.

  12. [Genetic characterization of populations of the Volga-Ural region according to the variability of the Y-chromosome].

    Science.gov (United States)

    Trofimova, N V; Litvinov, S S; Khusainova, R I; Penkin, L N; Akhmetova, V L; Akhatova, F S; Khusnutdinova, É K

    2015-01-01

    An analysis of genetic diversity in nine ethnic groups of the Volga-Ural region was carried out using 15 biallelic loci in the nonrecombining region of the Y-chromosome. The major Y-chromosome haplogroups in the region are R1a-M198, R1b-M269, and N-M231. It was found that Bashkirs show the greatest difference from other populations of the Volga-Ural region according both to F(st) and to the principal component analysis. In addition, analysis of the frequency distribution of Y-chromosome haplogroups was carried out in the Besermyan population, which was not studied previously from the Y-chromosome perspective. The results of this study revealed the predominance of haplogroup N-M231 (54.7%) in this ethnic group, which may indicate the prevalence of the Finno-Ugric component in the formation of the patrilineal component in the gene pool of the Besermyan ethnic group.

  13. Differential repetitive DNA composition in the centromeric region of chromosomes of Amazonian lizard species in the family Teiidae.

    Science.gov (United States)

    Carvalho, Natalia D M; Carmo, Edson; Neves, Rogerio O; Schneider, Carlos Henrique; Gross, Maria Claudia

    2016-01-01

    Differences in heterochromatin distribution patterns and its composition were observed in Amazonian teiid species. Studies have shown repetitive DNA harbors heterochromatic blocks which are located in centromeric and telomeric regions in Ameiva ameiva (Linnaeus, 1758), Kentropyx calcarata (Spix, 1825), Kentropyx pelviceps (Cope, 1868), and Tupinambis teguixin (Linnaeus, 1758). In Cnemidophorus sp.1, repetitive DNA has multiple signals along all chromosomes. The aim of this study was to characterize moderately and highly repetitive DNA sequences by C ot1-DNA from Ameiva ameiva and Cnemidophorus sp.1 genomes through cloning and DNA sequencing, as well as mapping them chromosomally to better understand its organization and genome dynamics. The results of sequencing of DNA libraries obtained by C ot1-DNA showed that different microsatellites, transposons, retrotransposons, and some gene families also comprise the fraction of repetitive DNA in the teiid species. FISH using C ot1-DNA probes isolated from both Ameiva ameiva and Cnemidophorus sp.1 showed these sequences mainly located in heterochromatic centromeric, and telomeric regions in Ameiva ameiva, Kentropyx calcarata, Kentropyx pelviceps, and Tupinambis teguixin chromosomes, indicating they play structural and functional roles in the genome of these species. In Cnemidophorus sp.1, C ot1-DNA probe isolated from Ameiva ameiva had multiple interstitial signals on chromosomes, whereas mapping of C ot1-DNA isolated from the Ameiva ameiva and Cnemidophorus sp.1 highlighted centromeric regions of some chromosomes. Thus, the data obtained showed that many repetitive DNA classes are part of the genome of Ameiva ameiva, Cnemidophorus sp.1, Kentroyx calcarata, Kentropyx pelviceps, and Tupinambis teguixin, and these sequences are shared among the analyzed teiid species, but they were not always allocated at the same chromosome position.

  14. Sex and age specific effects of chromosomal regions linked to body mass index in the Framingham Study

    Directory of Open Access Journals (Sweden)

    Fox Caroline S

    2006-01-01

    Full Text Available Abstract Background Previously, we reported significant linkage of body mass index (BMI to chromosomes 6 and 11 across six examinations, covering 28 years, of the Framingham Heart Study. These results were on all individuals available at each exam, thus the sample size varied from exam to exam. To remove any effect of sample size variation we have now constructed six subsets; for each exam individuals were only included if they were measured at every exam, i.e. for each exam, included individuals comprise the intersection of the original six exams. This strategy preferentially removed older individuals who died before reaching the sixth exam, thus the intersection datasets are smaller (n = 1114 and significantly younger than the full datasets. We performed variance components linkage analysis on these intersection datasets and on their sex-specific subsets. Results Results from the sex-specific genome scans revealed 11 regions in which a sex-specific maximum lodscore was at least 2.0 for at least one dataset. Randomization tests indicated that all 11 regions had significant (p Results from the full genome scans revealed that linked regions on chromosomes 6 and 11 remained significantly and consistently linked in the intersection datasets. Surprisingly, the maximum lodscore on chromosome 10 for dataset 1 increased from 0.97 in the older original dataset to 4.23 in the younger smaller intersection dataset. This difference in maximum lodscores was highly significant (p Conclusion Sex specific effects of chromosomal regions on BMI are common in the Framingham study. Some evidence also exists for age-specific effects of chromosomal regions.

  15. Normal phenotype and partial trisomy for the G positive region of chromosome 21.

    Science.gov (United States)

    Daniel, A

    1979-01-01

    A prenatally diagnosed male fetus and his mother, who was referred because of her advanced age, both carried an abnormal bisatellited chromosome 21 as an extra chromosome. The abnormal 21 was monocentric and the G negative band q22 and part of q21 had been deleted during formation. The phenotype of both the mother and child (at birth) was normal. Images PMID:157396

  16. Positional mapping of loci in the DiGeorge critical region at chromosome 22q11 using a new marker (D22S183)

    NARCIS (Netherlands)

    M. de Mulder (Maarten); M. Wilke (Martina); A. Langeveld (An); L.G. Wilming (Laurens); A. Hagemeijer (Anne); E. van Drunen (Ellen); E.C. Zwarthoff (Ellen); P.H.J. Riegman (Peter); W.H. Deelen (Wouter); A.M.W. van den Ouweland (Ans); D.J.J. Halley (Dicky); C. Meijers (Carel)

    1995-01-01

    textabstractThe majority of patients with DiGeorge syndrome (DGS) and velo-cardio-facial syndrome (VCFS) and a minority of patients with non-syndromic conotruncal heart defects are hemizygous for a region of chromosome 22q11. The chromosomal region that is commonly deleted is larger than 2 Mb. It ha

  17. Dissecting the transcriptional regulatory properties of human chromosome 16 highly conserved non-coding regions.

    Directory of Open Access Journals (Sweden)

    José Luis Royo

    Full Text Available Non-coding DNA conservation across species has been often used as a predictor for transcriptional enhancer activity. However, only a few systematic analyses of the function of these highly conserved non-coding regions (HCNRs have been performed. Here we use zebrafish transgenic assays to perform a systematic study of 113 HCNRs from human chromosome 16. By comparing transient and stable transgenesis, we show that the first method is highly inefficient, leading to 40% of false positives and 20% of false negatives. When analyzed in stable transgenic lines, a great majority of HCNRs were active in the central nervous system, although some of them drove expression in other organs such as the eye and the excretory system. Finally, by testing a fraction of the HCNRs lacking enhancer activity for in vivo insulator activity, we find that 20% of them may contain enhancer-blocking function. Altogether our data indicate that HCNRs may contain different types of cis-regulatory activity, including enhancer, insulators as well as other not yet discovered functions.

  18. A genetic linkage map of the diplosporous chromosomal region in Taraxacum officinale (common dandelion; Asteraceae).

    Science.gov (United States)

    Vijverberg, K; Van Der Hulst, R G M; Lindhout, P; Van Dijk, P J

    2004-02-01

    In this study, we mapped the diplosporous chromosomal region in Taraxacum officinale, by using amplified fragment length polymorphism technology (AFLP) in 73 plants from a segregating population. Taraxacum serves as a model system to investigate the genetics, ecology, and evolution of apomixis. The genus includes sexual diploid as well as apomictic polyploid, mostly triploid, plants. Apomictic Taraxacum is diplosporous, parthenogenetic, and has autonomous endosperm formation. Previous studies have indicated that these three apomixis elements are controlled by more than one locus in Taraxacum and that diplospory inherits as a dominant, monogenic trait ( Ddd; DIP). A bulked segregant analysis provided 34 AFLP markers that were linked to DIP and were, together with two microsatellite markers, used for mapping the trait. The map length was 18.6 cM and markers were found on both sides of DIP, corresponding to 5.9 and 12.7 cM, respectively. None of the markers completely co-segregated with DIP. Eight markers were selected for PCR-based marker development, of which two were successfully converted. In contrast to all other mapping studies of apomeiosis to date, our results showed no evidence for suppression of recombination around the DIP locus in Taraxacum. No obvious evidence for sequence divergence between the DIP and non- DIP homologous loci was found, and no hemizygosity at the DIP locus was detected. These results may indicate that apomixis is relatively recent in Taraxacum.

  19. Nucleolar organizer regions and a new chromosome number for Rhea americana (Aves: Rheiformes

    Directory of Open Access Journals (Sweden)

    Ricardo José Gunski

    1998-06-01

    Full Text Available Sequential banding analysis (Giemsa-C-banding-Ag NOR of chromosomes of the common rhea (Rhea americana was performed. Metaphases were obtained by peripheral blood lymphocyte culture and monolayer embryo cell culture. The diploid chromosome number was 80, different from the 2n = 82 in previous reports. Macrochromosome pairs 1, 2 and 5 were submetacentric and pair 3, subacrocentric. The 4th pair was acrocentric and all of the microchromosomes appeared to be acrocentric, with the exception of a clearly metacentric pair which was fully heterochromatic. The Z was slightly larger than the W, both being acrocentric and C-band negative. Nucleolar organizer regions were observed in the secondary constriction of a microchromosome pair. Correct identification of the NOR-bearing pair was possible only by sequential analyses, Giemsa staining followed by the Ag-NOR technique.Foram efetuadas análises seqüenciais de bandeamento cromossômico (Giemsa-banda-C-AgNOR em material da espécie Rhea americana (ema com o objetivo de identificar os cromossomos portadores de regiões organizadoras de nucléolos e confirmar o cariótipo desta espécie. As metáfases foram obtidas de culturas de leucócitos e de células de embrião. O número diplóide de cromossomos, determinado pela análise de metáfases oriundas de 19 espécimes, foi de 80 (2n = 80, NF = 95, o que difere da literatura. Os pares de macrocromossomos números 1, 2 e 5 eram submetacêntricos e o par 3 era sub-acrocêntrico, confirmado pelo bandeamento C. O par 4 era acrocêntrico, bem como todos os microcromossomos, com exceção de um metacêntrico inteiramente heterocromático. O cromossomo Z era ligeiramente maior que o W, sendo ambos acrocêntricos e banda-C negativos. A região organizadora de nucléolos foi observada na constrição secundária de um par de microcromossomos. A correta identificação do par portador da NOR só foi possível com a utilização da análise seqüencial de colora

  20. Identification of a short region on chromosome 6 affecting direct calving ease in Piedmontese cattle breed.

    Directory of Open Access Journals (Sweden)

    Silvia Bongiorni

    Full Text Available Calving in cattle is affected by calf morphology and by dam characteristics. It is described by two different traits: maternal calving ease, which is the ability to generate dams with good physiological predisposition to calving, and direct calving ease, which is the ability to generate calves that are easily born. The aim of this study was to identify regions of cattle genome harboring genes possibly affecting direct calving ease in the Piedmontese cattle breed. A population of 323 bulls scored for direct calving ease (EBV was analyzed by a medium-density SNP marker panel (54,001 SNPs to perform a genome-wide scan. The strongest signal was detected on chromosome 6 between 37.8 and 38.7 Mb where 13 SNPs associated to direct calving ease were found. Three genes are located in this region: LAP3, encoding for a leucine aminopeptidase involved in the oxytocin hydrolysis; NCAPG, encoding for a non-SMC condensin I complex, which has been associated in cattle with fetal growth and carcass size; and LCORL, which has been associated to height in humans and cattle. To further confirm the results of the genome-wide scan we genotyped additional SNPs within these genes and analyzed their association with direct calving ease. The results of this additional analysis fully confirmed the findings of the GWAS and particularly indicated LAP3 as the most probable gene involved. Linkage Disequilibrium (LD analysis showed high correlation between SNPs located within LAP3 and LCORL indicating a possible selection signature due either to increased fitness or breeders' selection for the trait.

  1. Loss of chromosome 1p/19q in oligodendroglial tumors: refinement of chromosomal critical regions and evaluation of internexin immunostaining as a surrogate marker.

    LENUS (Irish Health Repository)

    Buckley, Patrick G

    2011-03-01

    Loss of chromosome 1p\\/19q in oligodendrogliomas represents a powerful predictor of good prognosis. Expression of internexin (INA), a neuronal specific intermediate filament protein, has recently been proposed as a surrogate marker for 1p\\/19q deletion based on the high degree of correlation between both parameters in oligodendrogliomas. The aim of this study was to assess further the diagnostic utility of INA expression in a set of genetically well-characterized oligodendrogliomas. On the basis of a conservative approach for copy number determination, using both comparative genomic hybridization and fluorescent in situ hybridization, INA expression as a surrogate marker for 1p\\/19q loss had both reduced specificity (80%) and sensitivity (79%) compared with respective values of 86% and 96% reported in the previous report. The histologic interpretation and diagnostic value of INA expression in oligodendrogliomas should therefore be assessed with greater caution when compared with 1p\\/19q DNA copy number analysis. In addition, DNA copy number aberrations of chromosomes 10, 16, and 17 were detected exclusively in 1p\\/19q codeleted samples, suggesting that other regions of the genome may contribute to the 1p\\/19q-deleted tumor phenotype inthese samples.

  2. Mapping strategies: Chromosome 16 workshop

    Energy Technology Data Exchange (ETDEWEB)

    1989-01-01

    The following topics from a workshop on chromosome 16 are briefly discussed: genetic map of chromosome 16; chromosome breakpoint map of chromosome 16; integrated physical/genetic map of chromosome 16; pulsed field map of the 16p13.2--p13.3 region (3 sheets); and a report of the HGM10 chromosome 16 committee.

  3. Genetic isolation of a chromosome 1 region affecting susceptibility to hypertension-induced renal damage in the spontaneously hypertensive rat.

    Science.gov (United States)

    St Lezin, E; Griffin, K A; Picken, M; Churchill, M C; Churchill, P C; Kurtz, T W; Liu, W; Wang, N; Kren, V; Zidek, V; Pravenec, M; Bidani, A K

    1999-08-01

    Linkage studies in the fawn-hooded hypertensive rat have suggested that genes influencing susceptibility to hypertension-associated renal failure may exist on rat chromosome 1q. To investigate this possibility in a widely used model of hypertension, the spontaneously hypertensive rat (SHR), we compared susceptibility to hypertension-induced renal damage between an SHR progenitor strain and an SHR congenic strain that is genetically identical except for a defined region of chromosome 1q. Backcross breeding with selection for the markers D1Mit3 and Igf2 on chromosome 1 was used to create the congenic strain (designated SHR.BN-D1Mit3/Igf2) that carries a 22 cM segment of chromosome 1 transferred from the normotensive Brown Norway rat onto the SHR background. Systolic blood pressure (by radiotelemetry) and urine protein excretion were measured in the SHR progenitor and congenic strains before and after the induction of accelerated hypertension by administration of DOCA-salt. At the same level of DOCA-salt hypertension, the SHR.BN-D1Mit3/Igf2 congenic strain showed significantly greater proteinuria and histologically assessed renal vascular and glomerular injury than the SHR progenitor strain. These findings demonstrate that a gene or genes that influence susceptibility to hypertension-induced renal damage have been trapped in the differential chromosome segment of the SHR.BN-D1Mit3/Igf2 congenic strain. This congenic strain represents an important new model for the fine mapping of gene(s) on chromosome 1 that affect susceptibility to hypertension-induced renal injury in the rat.

  4. Y-Chromosomal Lineages of Latvians in the Context of the Genetic Variation of the Eastern-Baltic Region.

    Science.gov (United States)

    Pliss, Liana; Timša, Līga; Rootsi, Siiri; Tambets, Kristiina; Pelnena, Inese; Zole, Egija; Puzuka, Agrita; Sabule, Areta; Rozane, Sandra; Lace, Baiba; Kucinskas, Vaidutis; Krumina, Astrida; Ranka, Renate; Baumanis, Viesturs

    2015-11-01

    Variations of the nonrecombining Y-chromosomal region were investigated in 159 unrelated Baltic-speaking ethnic Latvians from four different geographic regions, using 28 biallelic markers and 12 short tandem repeats. Eleven different haplogroups (hgs) were detected in a regionally homogeneous Latvian population, among which N1c, R1a, and I1 cover more than 85% of its paternal lineages. When compared its closest geographic neighbors, the composition of the Latvian Y-chromosomal gene pool was found to be very similar to those of Lithuanians and Estonians. Despite the comparable frequency distribution of hg N1c in Latvians and Lithuanians with the Finno-Ugric-speaking populations from the Eastern coast of the Baltic Sea, the observed differences in allelic variances of N1c haplotypes between these two groups are in concordance with the previously stated hypothesis of different dispersal ways of this lineage in the region. More than a third of Latvian paternal lineages belong specifically to a recently defined R1a-M558 hg, indicating an influence from a common source within Eastern Slavic populations on the formation of the present-day Latvian Y-chromosome gene pool. © 2015 John Wiley & Sons Ltd/University College London.

  5. Directed isolation and mapping of microsatellites from swine Chromosome 1q telomeric region through microdissection and RH mapping.

    Science.gov (United States)

    Sarker, N; Hawken, R J; Takahashi, S; Alexander, L J; Awata, T; Schook, L B; Yasue, H

    2001-07-01

    Several quantitative trait loci (QTLs) (vertebrate number, birth weight, age at puberty, growth rate, gestation length, and backfat depth) have been independently mapped to the distal region of swine Chromosome (SSC) 1q in several resource populations. In order to improve the map resolution and refine these QTLs more precisely on SSC1q, we have isolated and mapped additional microsatellites (ms), using chromosome microdissection and radiation hybrid (RH) mapping. Five copies of the telomeric region of SSC1q were microdissected from metaphase spreads and pooled. The chromosomal fragment DNA was randomly amplified by using degenerate oligonucleotide primed polymerase chain reaction (DOP-PCR), enriched for ms, and subcloned into a PCR vector. Screening of subsequent clones with ms probes identified 23 unique ms sequences. Fifteen of these (65%) were subjected to radiation hybrid (RH) mapping by using the INRA-University of Minnesota porcine RH panel (IMpRH); and the remaining eight were not suited for the RH mapping. Twelve microsatellites were assigned to SSC1q telomeric region of IMpRH map (LOD >6), and three remain unlinked (LOD pig. In summary, we have used microdissection and radiation hybrid mapping to clone and map 12 new microsatellites to the swine gene map to increase the resolution of SSC1q in the region of known QTLs.

  6. Investigation of QTL regions on Chromosome 17 for genes associated with meat color in the pig.

    Science.gov (United States)

    Fan, B; Glenn, K L; Geiger, B; Mileham, A; Rothschild, M F

    2008-08-01

    Previous studies have uncovered several significant quantitative trait loci (QTL) relevant to meat colour traits mapped at the end of SSC17 in the pig. Furthermore, results released from the porcine genome sequencing project have identified genes underlying the entire QTL regions and can further contribute to mining the region for likely causative genes. Ten protein coding genes or novel transcripts located within the QTL regions were screened for single nucleotide polymorphisms (SNPs). Linkage mapping and association studies were carried out in the ISU Berkshire x Yorkshire (B x Y) pig resource family. The total length of the new SSC17 linkage map was 126.6 cM and additional markers including endothelin 3 (EDN3) and phosphatase and actin regulator 3 (PHACTR3) genes were assigned at positions 119.4 cM and 122.9 cM, respectively. A new QTL peak was noted at approximately 120 cM, close to the EDN3 gene, and for some colour traits QTL exceeded the 5% chromosome-wise significance threshold. The association analyses in the B x Y family showed that the EDN3 BslI and PHACTR3 PstI polymorphisms were strongly associated with the subjective colour score and objective colour reflectance measures in the loin, as well as average drip loss percentage and pH value. The RNPC1 DpnII and CTCFL HpyCH4III polymorphisms were associated with some meat colour traits. No significant association between CBLN4, TFAP2C, and four novel transcripts and meat colour traits were detected. The association analyses conducted in one commercial pig line found that both EDN3 BslI and PHACTR3 PstI polymorphisms were associated with meat colour reflectance traits such as centre loin hue angle and Minolta Lightness score. The present findings suggested that the EDN3 and PHACTR3 genes might have potential effects on meat colour in pigs, and molecular mechanisms of their functions are worth exploring.

  7. Long range chromosome organization in Escherichia coli: The position of the replication origin defines the non-structured regions and the Right and Left macrodomains

    Science.gov (United States)

    2017-01-01

    The Escherichia coli chromosome is organized into four macrodomains (Ori, Ter, Right and Left) and two non-structured regions. This organization influences the segregation of sister chromatids, the mobility of chromosomal DNA, and the cellular localization of the chromosome. The organization of the Ter and Ori macrodomains relies on two specific systems, MatP/matS for the Ter domain and MaoP/maoS for the Ori domain, respectively. Here by constructing strains with chromosome rearrangements to reshuffle the distribution of chromosomal segments, we reveal that the difference between the non-structured regions and the Right and Left lateral macrodomains relies on their position on the chromosome. A change in the genetic location of oriC generated either by an inversion within the Ori macrodomain or by the insertion of a second oriC modifies the position of Right and Left macrodomains, as the chromosome region the closest to oriC are always non-structured while the regions further away behave as macrodomain regardless of their DNA sequence. Using fluorescent microscopy we estimated that loci belonging to a non-structured region are significantly closer to the Ori MD than loci belonging to a lateral MD. Altogether, our results suggest that the origin of replication plays a prominent role in chromosome organization in E. coli, as it determines structuring and localization of macrodomains in growing cell. PMID:28486476

  8. Segmental Duplications in Euchromatic Regions of Human Chromosome 5: A Source of Evolutionary Instability and Transcriptional Innovation

    Science.gov (United States)

    Courseaux, Anouk; Richard, Florence; Grosgeorge, Josiane; Ortola, Christine; Viale, Agnes; Turc-Carel, Claude; Dutrillaux, Bernard; Gaudray, Patrick; Nahon, Jean-Louis

    2003-01-01

    Recent analyses of the structure of pericentromeric and subtelomeric regions have revealed that these particular regions of human chromosomes are often composed of blocks of duplicated genomic segments that have been associated with rapid evolutionary turnover among the genomes of closely related primates. In the present study, we show that euchromatic regions of human chromosome 5—5p14, 5p13, 5q13, 5q15–5q21—also display such an accumulation of segmental duplications. The structure, organization and evolution of those primate-specific sequences were studied in detail by combining in silico and comparative FISH analyses on human, chimpanzee, gorilla, orangutang, macaca, and capuchin chromosomes. Our results lend support to a two-step model of transposition duplication in the euchromatic regions, with a founder insertional event at the time of divergence between Platyrrhini and Catarrhini (25–35 million years ago) and an apparent burst of inter- and intrachromosomal duplications in the Hominidae lineage. Furthermore, phylogenetic analysis suggests that the chronology and, likely, molecular mechanisms, differ regarding the region of primary insertion—euchromatic versus pericentromeric regions. Lastly, we show that as their counterparts located near the heterochromatic region, the euchromatic segmental duplications have consistently reshaped their region of insertion during primate evolution, creating putative mosaic genes, and they are obvious candidates for causing ectopic rearrangements that have contributed to evolutionary/genomic instability. [Supplemental material is available online at www.genome.org. The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: D. Le Paslier, A. McKenzie, J. Melki, C. Sargent, J. Scharf and S. Selig.] PMID:12618367

  9. Identification and genetic mapping of a homeobox gene to the 4p16. 1 region of human chromosome 4

    Energy Technology Data Exchange (ETDEWEB)

    Stadler, H.S.; Padanilam, B.J.; Solursh, M. (Univ. of Iowa, Iowa City (United States)); Buetow, K. (Fox Chase Cancer Center, Philadelphia, PA (United States)); Murray, J.C. (Univ. of Iowa Hospitals and Clinics, Iowa City (United States))

    1992-12-01

    A human craniofacial cDNA library was screened with a degenerate oligonucleotide probe based on the conserved third helix of homeobox genes. From this screening, we identified a homeobox gene, H6, which shared only 57-65% amino acid identity to previously reported homeodomains. H6 was physically mapped to the 4P16.1 region by using somatic cell hybrids containing specific deletions of human chromosome 4. Linkage data from a single-stranded conformational polymorphism derived from the 3[prime] untranslated region of the H6 cDNA placed this homeobox gene more than 20 centimorgans proximal of the previously mapped HOX7 gene on chromosome 4. Identity comparisons of the H6 Homeodomain with previously reported homeodomains reveal the highest identities to be with the Nk class of homeobox genes in Drosophila melanogaster. 53 refs., 5 figs., 2 tabs.

  10. Identification and genetic mapping of a homeobox gene to the 4p16.1 region of human chromosome 4.

    Science.gov (United States)

    Stadler, H S; Padanilam, B J; Buetow, K; Murray, J C; Solursh, M

    1992-12-01

    A human craniofacial cDNA library was screened with a degenerate oligonucleotide probe based on the conserved third helix of homeobox genes. From this screening, we identified a homeobox gene, H6, which shared only 57-65% amino acid identity to previously reported homeodomains. H6 was physically mapped to the 4p16.1 region by using somatic cell hybrids containing specific deletions of human chromosome 4. Linkage data from a single-stranded conformational polymorphism derived from the 3' untranslated region of the H6 cDNA placed this homeobox gene more than 20 centimorgans proximal of the previously mapped HOX7 gene on chromosome 4. Identity comparisons of the H6 homeodomain with previously reported homeodomains reveal the highest identities to be with the Nk class of homeobox genes in Drosophila melanogaster.

  11. Chromosomal Q-heterochromatin regions in native highlanders of Pamir and Tien-Shan and in newcomers.

    Science.gov (United States)

    Ibraimov, A I; Kurmanova, G U; Ginsburg, E Kh; Aksenovich, T I; Aksenrod, E I

    1990-01-01

    The variability of human chromosomal Q-heterochromatin regions (Q-HR) was studied in 385 newcomers well adapted to the extreme environmental conditions of Pamir and Tien-Shan, as well as in 284 representatives of the native population of these regions. Newcomers were found to represent a highly homogeneous group as regards all the quantitative characteristics of Q-HR variability, but at the same time they differed significantly from both native residents and individuals of similar nationality (Russians) living permanently at low altitude. Differences between these three groups in the amount of Q-HRs in their genome are discussed as evidence in favour of the hypothesis of the possible selective value of chromosomal Q-heterochromatin material in human adaptation to extreme environmental high-altitude conditions.

  12. The spinal muscular atrophy gene region at 5q13.1 has a paralogous chromosomal region at 6p21.3.

    Science.gov (United States)

    Banyer, J L; Goldwurm, S; Cullen, L; van der Griend, B; Zournazi, A; Smit, D J; Powell, L W; Jazwinska, E C

    1998-03-01

    Paralogous regions are duplicated segments of chromosomal DNA that have been acquired during the evolution of the genome. Subsequent divergent evolution of the genes within paralogous regions can lead to the formation of gene families. Here, we report the identification of a region on Chromosome (Chr) 6 at 6p21.3 that is paralogous with the Spinal Muscular Atrophy (SMA) gene region on Chr 5 at 5q13.1. Partial characterization of this region identified nine sequences all of which are highly homologous to DNA sequences of the SMA gene region at 5q13.1. These sequences include four beta-glucuronidase sequences, two retrotransposon sequences, a novel cDNA, a Sequence Tagged Site (STS), and one that is homologous to exon 9 of the Neuronal Apoptosis Inhibitor Protein (NAIP) gene. The 6p21.3 paralogous SMA region may contain genes that are related to those in the SMA region at 5q13.1; however, a direct association of this region with SMA is unlikely given that no linkage of SMA with Chr 6 has been reported.

  13. Saethre-Chotzen syndrome with severe developmental delay associated with deletion of chromosomic region 7p15 --> pter.

    Science.gov (United States)

    Touliatou, V; Mavrou, A; Kolialexi, A; Kanavakis, E; Kitsiou-Tzeli, S

    2007-01-01

    Saethre-Chotzen syndrome represents one of the most common types of craniosynostosis inherited as an autosomal dominant disorder while sporadic cases have also been reported. It is characterized by high penetrance and variable expressivity, leading to difficulties in clinical diagnosis. Some patients, who exhibit most of the diagnostic criteria of Saethre-Chotzen syndrome, have structural abnormalities of chromosome 7. The case of a 4 year old boy with notable dysmorphic features compatible with Saethre-Chotzen syndrome and severe developmental delay is described. Conventional and molecular cytogenetic analysis of peripheral blood samples from the patient and his parents revealed partial monosomy of chromosomal region 7p15 --> pter de novo. The TWIST gene, located on chromosome 7p21.1, is thought to be a negative transcriptional regulator involved in osteoblast differentiation and maturation and it is thought that haploinsufficiency of the gene can cause the disorder. The diagnosis of Saethre-Chotzen syndrome and the identification of the chromosomal abnormality in the patient facilitated genetic counseling of the family.

  14. Genetic map of the spinocerebellar ataxia type 2 (SCA2) region on chromosome 12

    Energy Technology Data Exchange (ETDEWEB)

    Nechiporuk, A.; Frederick, T.; Pulst, S.M. [UCLA School of Medicine, Los Angeles, CA (United States)] [and others

    1994-09-01

    The autosomal dominant ataxias (SCAs) are a clinically and genetically heterogeneous group of neurodegenerative diseases characterized by progressive ataxia. At least four gene loci have been identified: SCA1 on chromosome (CHR) 6, SCA2 on CHR12, Machado-Joseph disease on CHR14, and SCA families that are not linked to any of the above loci. In addition, the gene causing dentato-rubro-pallido-luysian atrophy has been identified as an expanded CAG repeat on CHR 12p. As a necessary step in identifying the gene for SCA2, we now identified closer flanking markers. To do this we ordered microsatellite markers in the now identified closer flanking markers. To do this we ordered microsatellite markers in the region and then determined pairwise and multipoint lod scores between the markers and SCA2 in three large pedigrees with SCA. The following order was established with odds > 1,000:1 using six non-SCA pedigrees: D12S101-7.1cM-D12S58-0cM-IGF1-3.6cM-D12S78-1.4cM-D12S317-3.7cM-D12S84-0cM-D12S105-7.2cM-D12S79-7.0cM-PLA2. Using this ordered set of markers we examined linkage to SCA2 in three pedigrees of Italian, Austrian and French-Canadian descent. Pairwise linkage analysis resulted in significant positive lod scores for all markers. The highest pairwise lod score was obtained with D12S84/D12S105 (Z{sub max}=7.98, theta{sub max}=0.05). To further define the location of SCA2, we performed multipoint linkage analysis using the genetic map established above. The highest location score was obtained between D12S317 and D12S84/D12S105. A location of SCA2 between these loci was favored with odds > 100:1. These data likely narrow the SCA2 candidate region to approximately 3.7 cM. The relatively large large number of markers tightly linked to SCA2 will facilitate the assignment of additional SCA pedigrees to CHR12, and will help in the presymptomatic diagnosis of individuals in families with proven linkage to CHR12.

  15. Identification of 2nd chromosome region translocated onto the W chromosome by RFLP with EST-cDNA clones in the Gensei-kouken strains of the mulberry silkworm, Bombyx mori L

    Directory of Open Access Journals (Sweden)

    Sivaramakurup Sreekumar

    2010-01-01

    Full Text Available In silkworms, sex-limited strains are either obtained spontaneously or induced by X-rays or gamma rays. When a fragment of an autosome carrying a dominant allele of those genes responsible for certain characters is translocated onto a W chromosome, the female of the successive generations will express these phenotypic characters and sex discrimination can be facilitated. Gensei-kouken strains are sex-limited strains of silkworms developed by irradiating the pupae with gamma rays, by which a portion of the second chromosome is translocated onto the W chromosome. In these improved strains, the females are yellow-blooded and spin yellow cocoons. By using the EST-cDNA clones mapped on the Z chromosome, we identified the sex according to the polymorphic banding pattern or intensity of the signals. Furthermore, by using the clones on the second chromosome, the region of the second chromosome translocated onto the W chromosome was also defined. In both the A95 and A 96 strains selected for the present study, only the mid-portion of the second chromosome was translocated. The differences in length of the fragments translocated in these strains are discussed.

  16. A map of nuclear matrix attachment regions within the breast cancer loss-of-heterozygosity region on human chromosome 16q22.1

    DEFF Research Database (Denmark)

    Shaposhnikov, Sergey A.; Akopov, Sergey B.; Chernov, Igor P.

    2007-01-01

    There is abundant evidence that the DNA in eukaryotic cells is organized into loop domains that represent basic structural and functional units of chromatin packaging. To explore the DNA domain organization of the breast cancer loss-of-heterozygosity region on human chromosome 16q22.1, we have...... identified a significant portion of the scaffold/matrix attachment regions (S/MARs) within this region. Forty independent putative S/MAR elements were assigned within the 16q22.1 locus. More than 90% of these S/MARs are AT rich, with GC contents as low as 27% in 2 cases. Thirty-nine (98%) of the S...

  17. Exclusion of linkage between alcoholism and the MNS blood group region on chromosome 4q in multiplex families

    Energy Technology Data Exchange (ETDEWEB)

    Neiswanger, K.; Kaplan, B.; Hill, S.Y. [Univ. of Pittsburgh School of Medicine, PA (United States)

    1995-02-27

    Polymorphic DNA markers on the long arm of chromosome 4 were used to examine linkage to alcoholism in 20 multiplex pedigrees. Fifteen loci were determined for 124 individuals. Lod scores were calculated assuming both dominant and recessive disease modes of inheritance, utilizing incidence data by age and gender that allow for correction for variable age of onset and frequency of the disorder by gender. Under the assumption that alcoholism is homogeneous in this set of pedigrees, and that a recessive mode with age and gender correction is the most appropriate, the total lod scores for all families combined were uniformly lower than -2.0. This suggests an absence of linkage between the putative alcoholism susceptibility gene and markers in the region of the MNS blood group (4q28-31), a region for which we had previously found suggestive evidence of linkage to alcoholism. The 100 cM span of chromosome 4 studied includes the class I alcohol dehydrogenase (ADH) loci. Using the recessive mode, no evidence for linkage to alcoholism was found for the markers tested, which spanned almost the entire long arm of chromosome 4. Under the dominant mode, no evidence for linkage could be found for several of the markers. 36 refs., 1 fig., 3 tabs.

  18. Random search for shared chromosomal regions in four affected individuals: the assignment of a new hereditary ataxia locus

    Energy Technology Data Exchange (ETDEWEB)

    Nikali, K.; Suomalainen, A.; Koskinen, T.; Peltonen, L. [Univ. of Helsinki (Finland); Terwilliger, J. [Univ. of Oxford (United Kingdom); Weissenbach, J. [Genethon, Evry (France)

    1995-05-01

    Infantile-onset spinocerebellar ataxia (IOSCA) is an autosomal recessively inherited progressive neurological disorder of unknown etiology. This ataxia, identified so far only in the genetically isolated Finnish population, does not share gene locus with any of the previously identified hereditary ataxias, and a random mapping approach was adopted to assign the IOSCA locus. Based on the assumption of one founder mutation, a primary screening of the genome was performed using samples from just four affected individuals in two consanguineous pedigrees. The identification of a shared chromosomal region in these four patients provided the first evidence that the IOSCA gene locus is on chromosome 10q23.3-q24.1, which was confirmed by conventional linkage analysis in the complete family material. Strong linkage disequilibrium observed between IOSCA and the linked markers was utilized to define accurately the critical chromosomal region. The results showed the power of linkage disequilibrium in the locus assignment of diseases with very limited family materials. 30 refs., 3 figs., 2 tabs.

  19. A ninth locus (RP18) for autosomal dominant retinitis pigmentosa maps in the pericentromeric region of chromosome 1.

    Science.gov (United States)

    Xu, S Y; Schwartz, M; Rosenberg, T; Gal, A

    1996-08-01

    We studied a large Danish family of seven generations in which autosomal dominant retinitis pigmentosa (adRP), a heterogeneous genetic form of retinal dystrophy, was segregating. After linkage had been excluded to all known adRP loci on chromosomes 3q, 6p, 7p, 7q, 8q, 17p, 17q and 19q, a genome screening was performed. Positive lod scores suggestive of linkage with values ranging between Z = 1.58-5.36 at theta = 0.04-0.20 were obtained for eight loci on proximal 1p and 1q. Close linkage without recombination and a maximum lod score of 7.22 at theta = 0.00 was found between the adRP locus (RP18) in this family and D1S498 which is on 1q very near the centromere. Analysis of multiply informative meioses suggests that in this family D1S534 and D1S305 flank RP18 in interval 1p13-q23. No linkage has been found to loci from this chromosomal region in six other medium sized adRP families in which the disease locus has been excluded from all known chromosomal regions harbouring an adRP gene or locus suggesting that there is (at least) one further adRP locus to be mapped in the future.

  20. Chromosomal mapping of the human M6 genes

    Energy Technology Data Exchange (ETDEWEB)

    Olinsky, S.; Loop, B.T.; DeKosky, A. [Univ. of Pittsburgh, PA (United States)] [and others

    1996-05-01

    M6 is a neuronal membrane glycoprotein that may have an important role in neural development. This molecule was initially defined by a monoclonal antibody that affected the survival of cultured cerebellar neurons and the outgrowth of neurites. The nature of the antigen was discovered by expression cDNA cloning using this monoclonal antibody. Two distinct murine M6 cDNAs (designated M6a and M6b) whose deduced amino acid sequences were remarkably similar to that of the myelin proteolipid protein human cDNA and genomic clones encoding M6a and M6b and have characterized them by restriction mapping, Southern hybridization with cDNA probes, and sequence analysis. We have localized these genes within the human genome by FISH (fluorescence in situ hybridization). The human M6a gene is located at 4q34, and the M6b gene is located at Xp22.2 A number of human neurological disorders have been mapped to the Xp22 region, including Aicardi syndrome (MIM 304050), Rett syndrome (MIM 312750), X-linked Charcot-Marie-Tooth neuropathy (MIM 302801), and X-linked mental retardation syndromes (MRX1, MIM 309530). This raises the possibility that a defect in the M6b gene is responsible for one of these neurological disorders. 8 refs., 3 figs.

  1. Methylation profiling in individuals with uniparental disomy identifies novel differentially methylated regions on chromosome 15.

    NARCIS (Netherlands)

    Sharp, A.J.; Migliavacca, E.; Dupre, Y.; Stathaki, E.; Sailani, M.R.; Baumer, A.; Schinzel, A.; Mackay, D.J.; Robinson, D.O.; Cobellis, G.; Cobellis, L.; Brunner, H.G.; Steiner, B.; Antonarakis, S.E.

    2010-01-01

    The maternal and paternal genomes possess distinct epigenetic marks that distinguish them at imprinted loci. In order to identify imprinted loci, we used a novel method, taking advantage of the fact that uniparental disomy (UPD) provides a system that allows the two parental chromosomes to be studie

  2. Investigating Transfer of Large Chromosomal Regions Containing the Pathogenicity Locus Between Clostridium difficile Strains

    NARCIS (Netherlands)

    Brouwer, Mike; Mullany, P.; Allan, E.; Roberts, P.

    2016-01-01

    The genomes of all sequenced Clostridium difficile isolates contain multiple mobile genetic elements. The chromosomally located pathogenicity locus (PaLoc), encoding the cytotoxins TcdA and TcdB, was previously hypothesized to be a mobile genetic element; however, mobility was not demonstrated. Here

  3. Investigating Transfer of Large Chromosomal Regions Containing the Pathogenicity Locus Between Clostridium difficile Strains

    NARCIS (Netherlands)

    Brouwer, Mike; Mullany, P.; Allan, E.; Roberts, P.

    2016-01-01

    The genomes of all sequenced Clostridium difficile isolates contain multiple mobile genetic elements. The chromosomally located pathogenicity locus (PaLoc), encoding the cytotoxins TcdA and TcdB, was previously hypothesized to be a mobile genetic element; however, mobility was not demonstrated. Here

  4. Mapping of 5q35 chromosomal rearrangements within a genomically unstable region

    DEFF Research Database (Denmark)

    Buysse, Karen; Crepel, An; Menten, Björn

    2008-01-01

    BACKGROUND: Recent molecular studies of breakpoints of recurrent chromosome rearrangements revealed the role of genomic architecture in their formation. In particular, segmental duplications representing blocks of >1 kb with >90% sequence homology were shown to mediate non-allelic homologous reco...

  5. Involvement of the chromosomal region 11q13 in renal oncocytoma : Case report and literature review

    NARCIS (Netherlands)

    Neuhaus, C; Dijkhuizen, T; vandenBerg, E; Storkel, S; Stockle, M; Mensch, B; Huber, C; Decker, HJ

    Renal oncocytomas comprise a cytogenetically heterogeneous group of tumors consisting potentially of cytogenetic distinguishable subgroups. Review of the literature revealed loss of chromosome 1 and Y as a possible anomaly for at least one subset of oncocytomas. The frequent finding of

  6. A physical map of the chromosomal region determining O-antigen biosynthesis in Vibrio cholerae O1.

    Science.gov (United States)

    Ward, H M; Morelli, G; Kamke, M; Morona, R; Yeadon, J; Hackett, J A; Manning, P A

    1987-01-01

    We have previously described the cosmid cloning of the genes determining the biosynthesis of the Inaba and Ogawa O-antigens of the lipopolysaccharides of Vibrio cholerae O1 (Manning et al., 1986). By Southern hybridization analysis of chromosomal and cosmid DNA, and heteroduplex analysis between the clones we have been able to precisely define the region of contiguous chromosomal DNA in the vicinity of the O-antigen-encoding region. These data and comparison of end points of clones and of deletion derivatives demonstrate that at least 16 kb of a 19-kb SstI fragment is required to encode O-antigen biosynthesis. Expression of O-antigen is independent of the orientation of this SstI fragment with respect to cloning vectors suggesting that its regulatory region has been cloned intact. No detectable differences were observed in the restriction patterns of the Inaba and Ogawa coding regions implying that only minor changes are involved when serotype conversion (Inaba to Ogawa or vice versa) occurs. Bhaskaran [Ind. J. Med. Res. 47 (1959) 253-260] originally defined this region associated with O-antigen biosynthesis oag; however, to be consistent with other organisms [Hitchcock et al., J. Bacteriol. 166 (1986) 699-705], it is suggested this be changed to rfb.

  7. Cloning and deletion mapping of the recF dnaN region of the Escherichia coli chromosome.

    Science.gov (United States)

    Ream, L W; Clark, A J

    1983-09-01

    By cloning a 3.6-kb EcoRI fragment of the Escherichia coli chromosome with pBR322 we located more precisely recF relative to dnaN. By deletion mapping we localized functional recF to a 1.65-kb region of the cloned fragment and allowed rough mapping of the C terminus of dnaN. Cloned recF+, separated from functional flanking genes dnaN and gyrB, complemented chromosomal recF mutations presumably by coding for a cytodiffusible product. The protein encoded by dnaN was observed as a band on a polyacrylamide gel from minicells. Identification of a recF protein was not made.

  8. Exclusion of candidate genes from the chromosome 1q juvenile glaucoma region and mapping of the peripheral cannabis receptor gene (CNR2) to chromosome 1

    Energy Technology Data Exchange (ETDEWEB)

    Sunden, S.L.F.; Nichols, B.E.; Alward, W.L.M. [Univ. of Iowa, Iowa City, IA (United States)] [and others

    1994-09-01

    Juvenile onset primary open angle glaucoma has been mapped by linkage to 1q21-q31. Several candidate genes were evaluated in the same family used to identify the primary linkage. Atrionatriuretic peptide receptor A (NPR1) and laminin C1 (LAMC1) have been previously mapped to this region and could putatively play a role in the pathogenesis of glaucoma. A third gene, the peripheral cannabis receptor (CNR2) was not initially mapped in humans but was a candidate because of the relief that cannabis affords some patients with primary open angle glaucoma. Microsatellites associated with NPR1 and LAMC1 revealed multiple recombinations in affected members of this pedigree. CNR2 was shown to be on chromosome 1 by PCR amplification of a 150 bp fragment of the 3{prime} untranslated region in monochromosomal somatic cell hybrids (NIGMS panel No. 2). These primers also revealed a two allele single strand conformation polymorphism which showed multiple recombinants with juvenile onset primary open angle glaucoma in large pedigrees, segregating this disorder. The marker was then mapped to 1p34-p36 by linkage, with the most likely location between liver alkaline phosphatase (ALPL) and alpha-L-1 fucosidase (FUCA1).

  9. The first cytogenetic data on Strumigenys louisianae Roger, 1863 (Formicidae: Myrmicinae: Dacetini: the lowest chromosome number in the Hymenoptera of the neotropical region.

    Directory of Open Access Journals (Sweden)

    Ana Paula Alves-Silva

    Full Text Available In the present study, the first cytogenetic data was obtained for the ant species Strumigenys louisianae, from a genus possessing no previous cytogenetic data for the Neotropical region. The chromosome number observed was 2n = 4, all possessing metacentric morphology. Blocks rich in GC base pairs were observed in the interstitial region of the short arm of the largest chromosome pair, which may indicate that this region corresponds to the NORs. The referred species presented the lowest chromosome number observed for the subfamily Myrmicinae and for the Hymenoptera found in the Neotropical region. Observation of a low chromosome number karyotype has been described in Myrmecia croslandi, in which the occurrence of tandem fusions accounts for the most probable rearrangement for its formation. The accumulation of cytogenetic data may carry crucial information to ensure deeper understanding of the systematics of the tribe Dacetini.

  10. Engineered chromosome-based genetic mapping establishes a 3.7-Mb critical genomic region for Down syndrome-associated heart defects in mice

    OpenAIRE

    Liu, Chunhong; Morishima, Masae; Jiang,Xiaoling; Yu, Tao; Meng, Kai; Ray, Debjit; Pao, Annie; Ye, Ping; Parmacek, Michael S.; Yu, Y. Eugene

    2013-01-01

    Trisomy 21 (Down syndrome, DS) is the most common human genetic anomaly associated with heart defects. Based on evolutionary conservation, DS-associated heart defects have been modeled in mice. By generating and analyzing mouse mutants carrying different genomic rearrangements in human chromosome 21 (Hsa21) syntenic regions, we found the triplication of the Tiam1-Kcnj6 region on mouse chromosome 16 (Mmu16) resulted in DS-related cardiovascular abnormalities. In this study, we developed two ta...

  11. Mapping of the chromosome 1p36 region surrounding the Charcot-Marie-Tooth disease type 2A locus

    Energy Technology Data Exchange (ETDEWEB)

    Denton, P.; Gere, S.; Wolpert, C. [Duke Univ., Durham, NC (United States)] [and others

    1994-09-01

    Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathy. Although CMT2 is clinically indistinguishable from CMT1, the two forms can be differentiated by pathological and neurophysiological methods. We have established one locus, CMT2A on chromosome 1p36, and have established genetic heterogeneity. This locus maps to the region of the deletions associated with neuroblastoma. We have now identified an additional 11 CMT2 families. Three families are linked to chromosome 1p36 while six families are excluded from this region. Another six families are currently under analysis and collection. To date the CMT2A families represent one third of those CMT2 families examined. We have established a microdissection library of the 1p36 region which is currently being characterized for microsatellite repeats and STSs using standard hybridization techniques and a modified degenerate primer method. In addition, new markers (D1S253, D1S450, D1S489, D1S503, GATA27E04, and GATA4H04) placed in this region are being mapped using critical recombinants in the CEPH reference pedigrees. Fluorescent in situ hybridization (FISH) has been used to confirm mapping. A YAC contig is being assembled from the CEPH megabase library using STSs to isolate key YACs which are extended by vectorette end clone and Alu-PCR. These findings suggest that the CMT2 phenotype is secondary to at least two different genes and demonstrates further heterogeneity in the CMT phenotype.

  12. Peopling of the North Circumpolar Region--insights from Y chromosome STR and SNP typing of Greenlanders.

    Directory of Open Access Journals (Sweden)

    Jill Katharina Olofsson

    Full Text Available The human population in Greenland is characterized by migration events of Paleo- and Neo-Eskimos, as well as admixture with Europeans. In this study, the Y-chromosomal variation in male Greenlanders was investigated in detail by typing 73 Y-chromosomal single nucleotide polymorphisms (Y-SNPs and 17 Y-chromosomal short tandem repeats (Y-STRs. Approximately 40% of the analyzed Greenlandic Y chromosomes were of European origin (I-M170, R1a-M513 and R1b-M343. Y chromosomes of European origin were mainly found in individuals from the west and south coasts of Greenland, which is in agreement with the historic records of the geographic placements of European settlements in Greenland. Two Inuit Y-chromosomal lineages, Q-M3 (xM19, M194, L663, SA01 and L766 and Q-NWT01 (xM265 were found in 23% and 31% of the male Greenlanders, respectively. The time to the most recent common ancestor (TMRCA of the Q-M3 lineage of the Greenlanders was estimated to be between 4,400 and 10,900 years ago (y. a. using two different methods. This is in agreement with the theory that the North Circumpolar Region was populated via a second expansion of humans in the North American continent. The TMRCA of the Q-NWT01 (xM265 lineage in Greenland was estimated to be between 7,000 and 14,300 y. a. using two different methods, which is older than the previously reported TMRCA of this lineage in other Inuit populations. Our results indicate that Inuit individuals carrying the Q-NWT01 (xM265 lineage may have their origin in the northeastern parts of North America and could be descendants of the Dorset culture. This in turn points to the possibility that the current Inuit population in Greenland is comprised of individuals of both Thule and Dorset descent.

  13. Genetic and physical mapping of two centromere-proximal regions of chromosome IV in Aspergillus nidulans

    DEFF Research Database (Denmark)

    Aleksenko, Alexei Y.; Nielsen, Michael Lynge; Clutterbuck, A.J.

    2001-01-01

    The centromere-proximal portion of the chromosome was mapped physically using overlapping clones of a cosmid genomic library. Two contiguous segments of a physical map, based on restriction mapping of cosmid clones, were generated, together covering more than 0.4 Mb DNA. A reverse genetic mapping...... approach was used to establish a correlation between physical and genetic maps; i,e., marker genes were integrated into physically mapped segments and subsequently mapped by mitotic and meiotic recombination. The resulting data, together with additional classical genetic mapping, lead to a substantial...... revision of the genetic map of the chromosome, including the position of the centromere, Comparison of physical and genetic maps indicates that meiotic recombination is low in subcentromeric DNA, its frequency being reduced from 1 crossover per 0.8 Mb to approximately 1 crossover per 5 Mb per meiosis...

  14. Polymorphism analysis of microsatellites and construction of linkage map in part regions of four chromosomes in chicken

    Institute of Scientific and Technical Information of China (English)

    WANG Shouzhi; LI Hui; LI Ning; GAO Yu; DU Zhiqiang; GU Zhiliang; WANG Qigui; LI Zhihui; WANG Ying

    2007-01-01

    Based on chicken' consensus map issued in 2000, 17 microsatellites near 4 candidate genes such as IGF2, OBR, GDFS and APOA1 in 4 chromosomes (chromosome 5, 7, 8 and 24) were chosen for polymorphism analysis and construction of linkage map. Combining the technique of PCR and the fluorescent semi-automated detection, genome scanning was performed for 440 chickens, which was derived from China Agricultural University chicken resource families within three generations. The individuals of this resource families were genotyped. The results showed that the number of alleles ranged from 4 to 14; heterozygosity (H) of markers was between 0.3116 and 0.9148. Polymorphic information content (PIC) varied from 0.2672 to 0.8679. Microsatellites along with above-mentioned 4 candidate genes doing as general markers were used to construct linkage map. The spans of 4 linkage maps constructed in the part region of chromosome 5, 7, 8 and 24 were 263.5, 79.9, 206.2 and 104.2 cM, respectively. The order of markers was consistent with that of counterpart of reported consensus map. However, The spans of linkage map were larger than that of consensus map. The constructed linkage maps laid the foundation for mapping quantitative trait loci (QTL) responsible for economically important traits in chicken.

  15. Identification of a high frequency of chromosomal rearrangements in the centromeric regions of prostate cancer patients

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The aim of the present investigation was to study the major chromosomal aberrations (CA) like deletion, translocation,inversion and mosaic in prostate cancer patients of Tamilnadu, Southern India. Totally 45 blood samples were collected from various hospitals in Tamilnadu, Southern India. Equal numbers of normal healthy subjects were chosen after signing a consent form. Volunteers provided blood samples (5 ml) to establish leukocyte cultures. Cytogenetic studies were performed by using Giemsa-banding technique and finally the results were ensured by spectral karyotyping (SKY) technique. In the present investigation, major CA like deletion, translocation, inversion and mosaic were identified in experimental subjects. Results showed frequent CA in chromosomes 1, 3, 5, 6, 7, 9, 13, 16, 18 and X. In comparison with experimental subjects, the control subjects exhibited very low levels of major CA (P<0.05). In the present study, the high frequency of centromeric rearrangements indicates a potential role for mitotic irregularities associated with the centromere in prostate cancer tumorigenesis. Identification of chromosome alterations may be helpful in understanding the molecular basis of the disease in better manner.

  16. 4p16.3 microdeletions and microduplications detected by chromosomal microarray analysis: New insights into mechanisms and critical regions.

    Science.gov (United States)

    Bi, Weimin; Cheung, Sau-Wai; Breman, Amy M; Bacino, Carlos A

    2016-10-01

    Deletions in the 4p16.3 region cause Wolf-Hirschhorn syndrome, a well known contiguous microdeletion syndrome with the critical region for common phenotype mapped in WHSCR2. Recently, duplications in 4p16.3 were reported in three patients with developmental delay and dysmorphic features. Through chromosomal microarray analysis, we identified 156 patients with a deletion (n = 109) or duplication (n = 47) in 4p16.3 out of approximately 60,000 patients analyzed by Baylor Miraca Genetics Laboratories. Seventy-five of the postnatally detected deletions encompassed the entire critical region, 32 (43%) of which were associated with other chromosome rearrangements, including six patients (8%) that had a duplication adjacent to the terminal deletion. Our data indicate that Wolf-Hirschhorn syndrome deletions with an adjacent duplication occur at a higher frequency than previously appreciated. Pure deletions (n = 14) or duplications (n = 15) without other copy number changes distal to or inside the WHSCR2 were identified for mapping of critical regions. Our data suggest that deletion of the segment from 0.6 to 0.9 Mb from the terminus of 4p causes a seizure phenotype and duplications of a region distal to the previously defined smallest region of overlap for 4p16.3 microduplication syndrome are associated with neurodevelopmental problems. We detected seven Wolf-Hirschhorn syndrome deletions and one 4p16.3 duplication prenatally; all of the seven are either >8 Mb in size and/or associated with large duplications. In conclusion, our study provides deeper insight into the molecular mechanisms, the critical regions and effective prenatal diagnosis for 4p16.3 deletions/ duplications. © 2016 Wiley Periodicals, Inc.

  17. Molecular cytogenetic analysis of Inv Dup(15) chromosomes, using probes specific for the Pradar-Willi/Angelman syndrome region: Clinical implications

    Energy Technology Data Exchange (ETDEWEB)

    Leana-Cox, J. (Univ. of Maryland School of Medicine, Baltimore, MD (United States)); Jenkins, L. (Kaiser Permanente Medical Group, San Jose, CA (United States)); Palmer, C.G.; Plattner, R. (Indiana School of Medicine, Indianapolis, IN (United States)); Sheppard, L. (Palo Verde Laboratory, Inc., Chandler, AZ (United States)); Flejter, W.L. (Univ. of Michigan, Ann Arbor, MI (United States)); Zackowski, J. (Univ. of Florida Health Science Center, Gainsville, FL (United States)); Tsien, F. (Tulane Univ. School of Medicine, New Orleans, LA (United States)); Schwartz, S. (Case Western Reserve Univ., Cleveland, OH (United States))

    1994-05-01

    Twenty-seven cases of inverted duplications of chromosome 15 (inv dup[15]) were investigated by FISH with two DNA probes specific for the Prader-Willi syndrome/Angelman syndrome (PWS/AS) region on proximal 15q. Sixteen of the marker chromosomes displayed two copies of each probe, while in the remaining 11 markers no hybridization was observed. A significant association was found between the presence of this region and an abnormal phenotype (P<.01). This is the largest study to date of inv dup(15) chromosomes, that uses molecular cytogenetic methods and is the first to report a significant association between the presence of a specific chromosomal region in such markers and an abnormal phenotype. 30 refs., 1 fig., 4 tabs.

  18. Use of an intron length polymorphism to localize the tropoelastin gene to mouse Chromosome 5 in a region of linkage conservation with human Chromosome 7

    Energy Technology Data Exchange (ETDEWEB)

    Wydner, K.S.; Passmore, H.C. [Rutgers Univ., Piscataway, NJ (United States); Sechler, J.L.; Boyd, C.D. [UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ (United States)

    1994-09-01

    The complete coding sequence for mouse tropoelastin was obtained from overlapping reverse transcriptase polymerase chain reaction (PCR) amplimers. These cDNA fragments were derived from mouse tropoelastin mRNA using PCR oligomers complementary to conserved domains within rat tropoelastin mRNA. A comparison of coding domains of mouse and rat tropoelastin mRNA revealed a greater than 93% homology at the nucleotide level and over 96% similarity in the predicted amino acid sequence. PCR primers complementary to regions of the mouse tropoelastin mRNA were used to define a novel intron length polymorphism (ILP) within intron 8 of the mouse tropoelastin gene (Eln). This ILP proved to be informative in an intraspecific backcross in which genomic DNA samples from 75 backcross mice were used to map the tropoelastin gene to a position in the distal half of mouse chromosome 5. The linkage and genetic distances between Eln and the closest molecular markers used in this study are centromere-D5Mit95, D5Mit96-6.7 cM-Gus, Eln-4.0 cM-Zp3-telomere.

  19. Analysis of plant meiotic chromosomes by chromosome painting.

    Science.gov (United States)

    Lysak, Martin A; Mandáková, Terezie

    2013-01-01

    Chromosome painting (CP) refers to visualization of large chromosome regions, entire chromosome arms, or entire chromosomes via fluorescence in situ hybridization (FISH). For CP in plants, contigs of chromosome-specific bacterial artificial chromosomes (BAC) from the target species or from a closely related species (comparative chromosome painting, CCP) are typically applied as painting probes. Extended pachytene chromosomes provide the highest resolution of CP in plants. CP enables identification and tracing of particular chromosome regions and/or entire chromosomes throughout all meiotic stages as well as corresponding chromosome territories in premeiotic interphase nuclei. Meiotic pairing and structural chromosome rearrangements (typically inversions and translocations) can be identified by CP. Here, we describe step-by-step protocols of CP and CCP in plant species including chromosome preparation, BAC DNA labeling, and multicolor FISH.

  20. Identification and genetic mapping of a homeobox gene to the 4p16.1 region of human chromosome 4.

    OpenAIRE

    Stadler, H S; Padanilam, B J; Buetow, K; Murray, J.C.; Solursh, M

    1992-01-01

    A human craniofacial cDNA library was screened with a degenerate oligonucleotide probe based on the conserved third helix of homeobox genes. From this screening, we identified a homeobox gene, H6, which shared only 57-65% amino acid identity to previously reported homeodomains. H6 was physically mapped to the 4p16.1 region by using somatic cell hybrids containing specific deletions of human chromosome 4. Linkage data from a single-stranded conformational polymorphism derived from the 3' untra...

  1. Analysis of two novel cDNAs from the Smith-Magenis syndrome region on chromosome 17

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Z.Y.; Lee, C.C.; Jiralerspong, S. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-09-01

    Smith-Magenis syndrome (SMS) is a clinically recognizable multiple congenital anomaly/mental retardation syndrome associated with deletion of chromosome 17p11.2. To date, only one gene encoding snRNA U3 has been mapped to this region. Here we report the identification of two novel genes, designated 463 and B9, which have been mapped to the SMS region. A full-length cDNA corresponding to each of these genes has been cloned and sequenced. Deletion analysis has been conducted on somatic cell hybrids retaining the del(17)(p11.2) chromosome from each of 15 SMS patients by PCR of sequence tagged sites for the cDNAs and confirmed by Southern analysis. The gene 463 is deleted in 15/15 patients analyzed to date, whereas the gene B9 is deleted in 10/15 of the patients analyzed. Fluorescence in situ hybridization is used to analyze additional SMS patients for hemizygosity at these loci. A physical map of the region is being constructed to determine the relative location of these cDNAs within 17p11.2. Our studies to date, thus, suggest that although both genes 463 and B9 are located within 17p11.2, gene 463 is more likely to be associated with SMS. Complete and exhaustive definition of the critical interval is required to demonstrate the role and importance of gene 463 in SMS.

  2. Mapping autonomously replicating sequence elements in a 73-kb region of chromosome II of the fission yeast, Schizosaccharomyces pombe

    Indian Academy of Sciences (India)

    Vinay Kumar Srivastava; Dharani Dhar Dubey

    2007-08-01

    Autonomously replicating sequence (ARS) elements are the genetic determinants of replication origin function in yeasts. They can be easily identified as the plasmids containing them transform yeast cells at a high frequency. As the first step towards identifying all potential replication origins in a 73-kb region of the long arm of fission yeast chromosome II, we have mapped five new ARS elements using systematic subcloning and transformation assay. 2D analysis of one of the ARS plasmids that showed highest transformation frequency localized the replication origin activity within the cloned genomic DNA. All the new ARS elements are localized in two clusters in centromere proximal 40 kb of the region. The presence of at least six ARS elements, including the previously reported ars727, is suggestive of a higher origin density in this region than that predicted earlier using a computer based search.

  3. Validated context-dependent associations of coronary heart disease risk with genotype variation in the chromosome 9p21 region

    DEFF Research Database (Denmark)

    Lusk, Christine M; Dyson, Greg; Clark, Andrew G;

    2014-01-01

    Markers of the chromosome 9p21 region are regarded as the strongest and most reliably significant genome-wide association study (GWAS) signals for Coronary heart disease (CHD) risk; this was recently confirmed by the CARDIoGRAMplusC4D Consortium meta-analysis. However, while these associations...... genotypes in the 9p21 region were strongest in a sub-group of hypertensives. We subsequently validated the effect of the region in an independent sample from the Copenhagen City Heart Study. Our study suggests that marker SNPs identified as predictors of CHD risk in large population based GWAS may have...... their greatest utility in explaining risk of disease in particular sub-groups characterized by biological and environmental effects measured by the traditional CHD risk factors....

  4. Regional assignment of the human uroporphyrinogen III synthase (UROS) gene to chromosome 10q25.2----q26.3.

    Science.gov (United States)

    Astrin, K H; Warner, C A; Yoo, H W; Goodfellow, P J; Tsai, S F; Desnick, R J

    1991-05-01

    Uroporphyrinogen III synthase [UROS; hydroxymethylbilane hydro-lyase (cyclizing), EC 4.2.1.75] is the fourth enzyme in the human heme biosynthetic pathway. The recent isolation of the cDNA encoding human UROS facilitated its chromosomal localization. Human UROS sequences were specifically amplified by the polymerase chain reaction (PCR) from genomic DNA of two independent panels of human-rodent somatic cell hybrids. There was 100% concordance for the presence of the human UROS PCR product and human chromosome 10. For each of the other chromosomes, there was 19%-53% discordance with human UROS. The chromosomal assignment was confirmed by Southern hybridization analysis of DNA from somatic cell hybrids with the full-length UROS cDNA. Using human-rodent hybrids containing different portions of human chromosome 10, we assigned the UROS gene to the region 10q25.2----q26.3.

  5. A 1.6-Mb P1-based physical map of the Down syndrome region on chromosome 21

    Energy Technology Data Exchange (ETDEWEB)

    Ohira, Miki; Suzuki, Kazunobu [National Cancer Center Research Institute, Tokyo (Japan)]|[Kazusa DNA Research Institute, Chiba (Japan); Ichikawa, Hitoshi [National Cancer Center Research Institute, Tokyo (Japan)] [and others

    1996-04-01

    The Down Syndrome (DS) region on chromosome 21, which is responsible for the main features of DS such as characteristic facial features, a congenital heart defect, and mental retardation, has been defined by molecular analysis of DS patients with partial trisomy 21. The 2.5-Mb region around the marker D21S55 between D21S17 and ERG in 21q22 is thought to be important, although contributions of other regions cannot be excluded. In this region, we focused on a 1.6-Mb region between a NotI site, LA68 (D21S396, which is mapped distal to D21S17) and ERG, because analysis of a Japanese DS family with partial trisomy 21 revealed that the proximal border of its triplicated region was distal to LA68. We constructed P1 contigs with 46 P1 clones covering more than 95% of the 1.6-Mb region. A high-resolution restriction map using BamHI was also constructed for more details analysis. Our P1 contig map supplements other physical maps previously reported and provides useful materials for further analysis including isolation and sequencing of the DS region. 31 refs., 7 figs., 1 tab.

  6. A Meiotic Drive Element in the Maize Pathogen Fusarium verticillioides Is Located Within a 102 kb Region of Chromosome V.

    Science.gov (United States)

    Pyle, Jay; Patel, Tejas; Merrill, Brianna; Nsokoshi, Chabu; McCall, Morgan; Proctor, Robert H; Brown, Daren W; Hammond, Thomas M

    2016-08-09

    Fusarium verticillioides is an agriculturally important fungus because of its association with maize and its propensity to contaminate grain with toxic compounds. Some isolates of the fungus harbor a meiotic drive element known as Spore killer (Sk(K)) that causes nearly all surviving meiotic progeny from an Sk(K) × Spore killer-susceptible (Sk(S)) cross to inherit the Sk(K) allele. Sk(K) has been mapped to chromosome V but the genetic element responsible for meiotic drive has yet to be identified. In this study, we used cleaved amplified polymorphic sequence markers to genotype individual progeny from an Sk(K) × Sk(S) mapping population. We also sequenced the genomes of three progeny from the mapping population to determine their single nucleotide polymorphisms. These techniques allowed us to refine the location of Sk(K) to a contiguous 102 kb interval of chromosome V, herein referred to as the Sk region. Relative to Sk(S) genotypes, Sk(K) genotypes have one extra gene within this region for a total of 42 genes. The additional gene in Sk(K) genotypes, herein named SKC1 for Spore Killer Candidate 1, is the most highly expressed gene from the Sk region during early stages of sexual development. The Sk region also has three hyper-variable regions, the longest of which includes SKC1 The possibility that SKC1, or another gene from the Sk region, is an essential component of meiotic drive and spore killing is discussed.

  7. The orphan nuclear receptor ROR{alpha} (RORA) maps to a conserved region of homology on human chromosome 15q21-q22 and mouse chromosome 9

    Energy Technology Data Exchange (ETDEWEB)

    Giguere, V. [McGill Univ., Montreal (Canada); Beatty, B.; Squire, J. [Hospital for Sick Children, Toronto (Canada)] [and others

    1995-08-10

    ROR{alpha} is a novel member of the steroid/thyroid/retinoid receptor superfamily with unique DNA-binding properties. We have mapped the RORA gene by fluorescence in situ hybridization to human chromosome 15q21-q22. To map the mouse Rora gene, a partial mouse cDNA clone was isolated from brain. Using interspecific backcross analysis, we have mapped the Rora gene to mouse chromosome 9. This places the human RORA gene in the proximity of the PML gene, which is involved in a reciprocal chromosomal translocation t(15:17) with the RARA gene in patients with acute promyelocytic leukemia. 13 refs., 2 figs.

  8. Localization of the human indoleamine 2,3-dioxygenase (IDO) gene to the pericentromeric region of human chromosome 8

    Energy Technology Data Exchange (ETDEWEB)

    Burkin, D.J.; Jones, C. (Eleanor Roosevelt Institute for Cancer Research, Denver, CO (United States)); Kimbro, K.S.; Taylor, M.W. (Indiana Univ., Bloomington, IN (United States)); Barr, B.L.; Gupta, S.L. (Hipple Cancer Research Center, Dayton, OH (United States))

    1993-07-01

    Indoleamine 2,3-dioxygenase (IDO) is the first enzyme in the catabolic pathway for tryptophan. This extrahepatic enzyme differs from the hepatic enzyme, tryptophan 2,3-dioxygenase (TDO), in molecular as well as enzymatic characteristics, although both enzymes catalyze the same reaction: cleavage of tryptophan into N-formylkynurenine. The induction of IDO by IFN-[gamma] plays a role in the antigrowth effect of IFN-[gamma] in cell cultures and in the inhibition of intracellular pathogens, e.g., Toxoplasma gondii and Chlamydia psittaci. Tryptophan is also the precursor for the synthesis of serotonin, and reduced levels of tryptophan and serotonin found in AIDS patients have been correlated with the presence of IFN-[gamma] and consequent elevation of IDO activity. The IDO enzyme has been purified and characterized, and its cDNA and genomic DNA clones have been isolated and analyzed. DNA from hybrid cells containing fragments of human chromosome 8 was used to determine the regional localization of the IDO gene on chromosome 8. The hybrids R30-5B and R30-2A contain 8p11 [yields] qter and 8q13 [yields] qter, respectively. Hybrid 229-3A contains the 8pter [yields] q11. The hybrid R30-2A was negative for the IDO gene, whereas R30-5B and 229-3A were positive as analyzed by PCR and verified by Southern blotting. Only the region close to the centromere is shared by R30-5B and 229-3A hybrids. The results indicate that the IDO gene is located on chromosome 8p11 [yields] q11.

  9. Cytogenetic analysis chromosomal status of subjects from the regions in the vicinity of uranium-contaminated areas

    Energy Technology Data Exchange (ETDEWEB)

    Jovicic, D.; Milacie, S.; Kovacevic, R.; Petrovic, I.

    2004-07-01

    The past application of nuclear technology has brought about free emission of numerous Due to the military application of the depleted uranium (DU) in our country, the problem of its radioactivity and hemo toxicity if actualized. Likewise every heavy metal, its is highly toxic and, in addition to it, also radioactive: Interaction of the water-soluble uranium forms with soil is an important effect. In this way, it penetrates into food chain and endangers human health. The study was aimed at determining possible karyotype genotoxic effects in individuals from the regions close to the contaminated areas. Biological dosimetry was performed using modified Moorthead's micromethod. Our studies included the targeted group of 29 patients from the affected regions. The subjects were averagely aged 39.5{+-}2.8 years. Average age of the control group (k), unexposed to the effects of the known genotoxic agents comprising 22 individuals was 28.3{+-}1.2 years. The presented data evidenced that increased incidence of the chromosomal aberrations was found in 6 subjects,accounting for 20.6%. Dicentric type changes were evidence, as well ring chromosomes and eccentric fragments, which are, at the same time the most frequent aberrations. The changes are considered reparable aberrations accounting for 2-3% in metaphases of the unexposed individuals. Statistical data processing evidenced significant difference (p<0.005) between structural chromosomal aberrations in the studied and control groups, as well as in the number of chromatid aberrations (p<0.05).Based on the obtained data it may be concluded that human karyotype changes were present in the studied group, resulting from interaction of ionizing irradiation and other genotoxic agents, with possibility of potent synergistic effects. It is necessary to stress the importance of further monitoring and control of the general population health, particularly due to possible late genetic effects that may affect future generations

  10. Identification of Chromosome Abnormalities in Subtelomeric Regions by Microarray Analysis: A Study of 5,380 Cases

    Science.gov (United States)

    Shao, Lina; Shaw, Chad A.; Lu, Xin-Yan; Sahoo, Trilochan; Bacino, Carlos A.; Lalani, Seema R.; Stankiewicz, Pawel; Yatsenko, Svetlana A.; Li, Yinfeng; Neill, Sarah; Pursley, Amber N.; Chinault, A. Craig; Patel, Ankita; Beaudet, Arthur L.; Lupski, James R.; Cheung, Sau W.

    2009-01-01

    Subtelomeric imbalances are a significant cause of congenital disorders. Screening for these abnormalities has traditionally utilized GTG-banding analysis, fluorescence in situ hybridization (FISH) assays, and multiplex ligation-dependent probe amplification. Microarray-based comparative genomic hybridization (array-CGH) is a relatively new technology that can identify microscopic and submicroscopic chromosomal imbalances. It has been proposed that an array with extended coverage at subtelomeric regions could characterize subtelomeric aberrations more efficiently in a single experiment. The targeted arrays for chromosome microarray analysis (CMA), developed by Baylor College of Medicine, have on average 12 BAC/PAC clones covering 10 Mb of each of the 41 subtelomeric regions. We screened 5,380 consecutive clinical patients using CMA. The most common reasons for referral included developmental delay (DD), and/or mental retardation (MR), dysmorphic features (DF), multiple congenital anomalies (MCA), seizure disorders (SD), and autistic, or other behavioral abnormalities. We found pathogenic rearrangements at subtelomeric regions in 236 patients (4.4%). Among these patients, 103 had a deletion, 58 had a duplication, 44 had an unbalanced translocation, and 31 had a complex rearrangement. The detection rates varied among patients with a normal karyotype analysis (2.98%), with an abnormal karyotype analysis (43.4%), and with an unavailable or no karyotype analysis (3.16%). Six patients out of 278 with a prior normal subtelomere-FISH analysis showed an abnormality including an interstitial deletion, two terminal deletions, two interstitial duplications, and a terminal duplication. In conclusion, genomic imbalances at subtelomeric regions contribute significantly to congenital disorders. Targeted array-CGH with extended coverage (up to 10 Mb) of subtelomeric regions will enhance the detection of subtelomeric imbalances, especially for submicroscopic imbalances. PMID

  11. Breakpoint regions and homologous synteny blocks in chromosomes have different evolutionary histories.

    Science.gov (United States)

    Larkin, Denis M; Pape, Greg; Donthu, Ravikiran; Auvil, Loretta; Welge, Michael; Lewin, Harris A

    2009-05-01

    The persistence of large blocks of homologous synteny and a high frequency of breakpoint reuse are distinctive features of mammalian chromosomes that are not well understood in evolutionary terms. To gain a better understanding of the evolutionary forces that affect genome architecture, synteny relationships among 10 amniotes (human, chimp, macaque, rat, mouse, pig, cattle, dog, opossum, and chicken) were compared at 20 Mbp) that are larger than expected by chance. Gene network analysis of msHSBs >3 human-Mbp and EBRs genes involved in development of the central nervous and other organ systems, whereas EBRs are enriched for genes associated with adaptive functions. In addition, we found EBRs are significantly enriched for structural variations (segmental duplications, copy number variants, and indels), retrotransposed and zinc finger genes, and single nucleotide polymorphisms. These results demonstrate that chromosome breakage in evolution is nonrandom and that HSBs and EBRs are evolving in distinctly different ways. We suggest that natural selection acts on the genome to maintain combinations of genes and their regulatory elements that are essential to fundamental processes of amniote development and biological organization. Furthermore, EBRs may be used extensively to generate new genetic variation and novel combinations of genes and regulatory elements that contribute to adaptive phenotypes.

  12. Delineation of a deletion region critical for corpus callosal abnormalities in chromosome 1q43-q44.

    Science.gov (United States)

    Nagamani, Sandesh C Sreenath; Erez, Ayelet; Bay, Carolyn; Pettigrew, Anjana; Lalani, Seema R; Herman, Kristin; Graham, Brett H; Nowaczyk, Malgorzata Jm; Proud, Monica; Craigen, William J; Hopkins, Bobbi; Kozel, Beth; Plunkett, Katie; Hixson, Patricia; Stankiewicz, Pawel; Patel, Ankita; Cheung, Sau Wai

    2012-02-01

    Submicroscopic deletions involving chromosome 1q43-q44 result in cognitive impairment, microcephaly, growth restriction, dysmorphic features, and variable involvement of other organ systems. A consistently observed feature in patients with this deletion are the corpus callosal abnormalities (CCAs), ranging from thinning and hypoplasia to complete agenesis. Previous studies attempting to delineate the critical region for CCAs have yielded inconsistent results. We conducted a detailed clinical and molecular characterization of seven patients with deletions of chromosome 1q43-q44. Using array comparative genomic hybridization, we mapped the size, extent, and genomic content of these deletions. Four patients had CCAs, and shared the smallest region of overlap that contains only three protein coding genes, CEP170, SDCCAG8, and ZNF238. One patient with a small deletion involving SDCCAG8 and AKT3, and another patient with an intragenic deletion of AKT3 did not have any CCA, implying that the loss of these two genes is unlikely to be the cause of CCA. CEP170 is expressed extensively in the brain, and encodes for a protein that is a component of the centrosomal complex. ZNF238 is involved in control of neuronal progenitor cells and survival of cortical neurons. Our results rule out the involvement of AKT3, and implicate CEP170 and/or ZNF238 as novel genes causative for CCA in patients with a terminal 1q deletion.

  13. Induction of micronuclei, hyperdiploidy and chromosomal breakage affecting the centric/pericentric regions of chromosomes 1 and 9 in human amniotic fluid cells after treatment with asbestos and ceramic fibers.

    Science.gov (United States)

    Dopp, E; Schuler, M; Schiffmann, D; Eastmond, D A

    1997-06-09

    This article describes the induction of micronuclei, hyperdiploidy and chromosome breakage in human amniotic cells in vitro by amosite, chrysotile and crocidolite asbestos, and ceramic fibers. The response of human (amniotic fluid cells) and rodent (Syrian hamster embryo fibroblasts, SHE) cells to fiber treatment was compared using the micronucleus assay. The data of the rodent studies were taken from a previous investigation (Dopp, E. et al. (1995) Environ. Health Perspect., 103, 268-271). All types of mineral fibers caused a significant increase of micronucleated cells. The kinetochore analysis revealed that all three types of asbestos and ceramic fibers yielded similar effects. Approximately 50% of the induced micronuclei were kinetochore-negative indicating formation through clastogenic events. Human amniotic cells were much less susceptible than SHE cells to the induction of micronuclei by mineral fibers. This again demonstrates that SHE cells are more susceptible to chromosomal changes than human amniotic fluid cells. The application of fluorescence in situ hybridization (FISH) with tandem DNA probes yielded more detailed information about specific structural chromosome aberrations in the 1 (cen-q12) and 9 (cen-q12) regions and about abnormal numbers of chromosomes in interphase human amniotic fluid cells. Using this FISH approach we found a statistically significant increase of chromosomal breakage in the pericentric heterochromatin regions of chromosomes 1 and 9 in interphase human amniotic cells after exposure to asbestos and ceramic fibers compared to control cells. The number of hyperdiploid cells was also significantly increased. Our results show that asbestos fibers as well as ceramic fibers are inducers of structural and numerical chromosomal aberrations in human amniotic fluid cells.

  14. A small XY chromosomal region explains sex determination in wild dioecious V. vinifera and the reversal to hermaphroditism in domesticated grapevines

    OpenAIRE

    Picq, Sandrine; Santoni, Sylvain; Lacombe, Thierry; Latreille, Muriel; Weber, Audrey; Ardisson, Morgane; Ivorra, Sarah; Maghradze, David; Arroyo-Garcia, Rosa; Chatelet, Philippe; This, Patrice; Terral, Jean-Fédéric; Bacilieri, Roberto

    2014-01-01

    Publis014-agap-029; Background In Vitis vinifera L., domestication induced a dramatic change in flower morphology: the wild sylvestris subspecies is dioecious while hermaphroditism is largely predominant in the domesticated subsp. V. v. vinifera. The characterisation of polymorphisms in genes underlying the sex-determining chromosomal region may help clarify the history of domestication in grapevine and the evolution of sex chromosomes in plants. In the genus Vitis, sex determination is putat...

  15. Levels and patterns of nucleotide variation in domestication QTL regions on rice chromosome 3 suggest lineage-specific selection.

    Directory of Open Access Journals (Sweden)

    Xianfa Xie

    Full Text Available Oryza sativa or Asian cultivated rice is one of the major cereal grass species domesticated for human food use during the Neolithic. Domestication of this species from the wild grass Oryza rufipogon was accompanied by changes in several traits, including seed shattering, percent seed set, tillering, grain weight, and flowering time. Quantitative trait locus (QTL mapping has identified three genomic regions in chromosome 3 that appear to be associated with these traits. We would like to study whether these regions show signatures of selection and whether the same genetic basis underlies the domestication of different rice varieties. Fragments of 88 genes spanning these three genomic regions were sequenced from multiple accessions of two major varietal groups in O. sativa--indica and tropical japonica--as well as the ancestral wild rice species O. rufipogon. In tropical japonica, the levels of nucleotide variation in these three QTL regions are significantly lower compared to genome-wide levels, and coalescent simulations based on a complex demographic model of rice domestication indicate that these patterns are consistent with selection. In contrast, there is no significant reduction in nucleotide diversity in the homologous regions in indica rice. These results suggest that there are differences in the genetic and selective basis for domestication between these two Asian rice varietal groups.

  16. Microhomology-mediated microduplication in the y chromosomal azoospermia factor a region in a male with mild asthenozoospermia.

    Science.gov (United States)

    Katsumi, Momori; Ishikawa, Hiromichi; Tanaka, Yoko; Saito, Kazuki; Kobori, Yoshitomo; Okada, Hiroshi; Saito, Hidekazu; Nakabayashi, Kazuhiko; Matsubara, Yoichi; Ogata, Tsutomu; Fukami, Maki; Miyado, Mami

    2014-01-01

    Y chromosomal azoospermia factor (AZF) regions AZFa, AZFb and AZFc represent hotspots for copy number variations (CNVs) in the human genome; yet the number of reports of AZFa-linked duplications remains limited. Nonallelic homologous recombination has been proposed as the underlying mechanism of CNVs in AZF regions. In this study, we identified a hitherto unreported microduplication in the AZFa region in a Japanese male individual. The 629,812-bp duplication contained 22 of 46 exons of USP9Y, encoding the putative fine tuner of spermatogenesis, together with all exons of 3 other genes/pseudogenes. The breakpoints of the duplication resided in the DNA/TcMar-Tigger repeat and nonrepeat sequences, respectively, and were associated with a 2-bp microhomology, but not with short nucleotide stretches. The breakpoint-flanking regions were not enriched with GC content, palindromes, or noncanonical DNA structures. Semen analysis of the individual revealed a normal sperm concentration and mildly reduced sperm motility. The paternal DNA sample of the individual was not available for genetic analysis. The results indicate that CNVs in AZF regions can be generated by microhomology-mediated break-induced replication in the absence of known rearrangement-inducing DNA features. AZFa-linked microduplications likely permit production of a normal amount of sperm, although the precise clinical consequences of these CNVs await further investigation.

  17. Adipose and muscle tissue expression of two genes (NCAPG and LCORL) located in a chromosomal region associated with cattle feed intake and gain

    Science.gov (United States)

    A region on bovine chromosome 6 has been implicated in cattle birth weight, growth, and length. Non-SMC conodensin I complex subunit G (NCAPG) and ligand dependent nuclear receptor corepressor-like protein (LCORL) are positional candidate genes within this region. We previously identified genetic ...

  18. Screening of YAC clones and building a map of the chromosome 13 region often deleted during chronic B-cell lymphocytic leucosis

    NARCIS (Netherlands)

    Brodyanskii, VM; Sulimova, GE; Udina, IG; Aitova, SS; Shaikhaev, GO; Sharikova, OA; Zakharev, VM; Fedorova, LI; Zelenin, AV; Eikhorn, S; Baush, C; Laland, M; Ross, M; Yankovskii, NK

    1995-01-01

    Pools of YAC clones from the ICRF library were analyzed by PCR using PBKpt, MGG15, and D13S25 markers that flank the chromosome 13 region often deleted during chronic lymphocytic leukemia. Ten clones were found and described. Nine mega-YAC clones from the CEPH library flanking the region of interest

  19. Yeast artificial chromosome contigs reveal that distal variable-region genes reside at least 3 megabases from the joining regions in the murine immunoglobulin kappa locus.

    Science.gov (United States)

    George, J B; Li, S; Garrard, W T

    1995-01-01

    The immunoglobulin kappa gene locus encodes 95% of the light chains of murine antibody molecules and is thought to contain up to 300 variable (V kappa)-region genes generally considered to comprise 20 families. To delineate the locus we have isolated 29 yeast artificial chromosome genomic clones that form two contigs, span > 3.5 megabases, and contain two known non-immunoglobulin kappa markers. Using PCR primers specific for 19 V kappa gene families and Southern analysis, we have refined the genetically defined order of these V kappa gene families. Of these, V kappa 2 maps at least 3.0 Mb from the joining (J kappa) region and appears to be the most distal V kappa gene segment. Images Fig. 3 Fig. 4 PMID:8618913

  20. Linkage between stature and a region on chromosome 20 and analysis of a candidate gene, bone morphogenetic protein 2

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, D.B.; Ossowski, V.; Janssen, R.C.; Knowler, W.C.; Bogardus, C. [National Inst. of Health, Phoenix, AZ (United States)

    1995-12-04

    Sib-pair linkage analysis of the quantitative trait, stature, in over 500 Pima Indians indicates that a genetic determinant of governing stature is located on chromosome 20. Analysis of 10 short tandem repeat polymorphisms localized this linkage to a 3. cM region that includes D20S98 and D20S66. Using all possible sib-pair combinations, linkage was detected to both stature (P = 0.0001) and to leg length (P = 0.001), but not to sitting height. Single-strand conformational polymorphism analysis of exon 3 of the bone morphogenetic protein 2 (BMP2) gene, a candidate gene in this region, in genomic DNA of 20 of the tallest and 20 of the shortest individuals did not show any consistent differences associated with leg length or height. Sequence analysis of the region encoding the mature protein revealed a single nucleotide substitution, a T to G transversion, not detected by single-strand conformational polymorphism (SSCP) analysis. This transversion results in a conservative amino acid substitution of glycine for valine at codon 80 of BMP2. The frequency of this allele was 0.23 in the sample. No significant differences in height were noted in persons carrying either allele. This indicates that this structural alteration in the mature BMP2 protein does not contribute to the differences in stature observed in the Pima Indians, nor is this structural change in the mature protein likely to be responsible for the linkage observed with stature on chromosome 20. 33 refs., 2 figs., 2 tabs.

  1. Evidence of a locus for orofacial clefting on human chromosome 6p24 and STS content map of the region.

    Science.gov (United States)

    Davies, A F; Stephens, R J; Olavesen, M G; Heather, L; Dixon, M J; Magee, A; Flinter, F; Ragoussis, J

    1995-01-01

    Orofacial clefting is genetically complex, no single gene being responsible for all forms. It can, however, result from a single gene defect either as part of a syndrome (e.g. van der Woude syndrome, Treacher-Collins syndrome, velo-cardio-facial syndrome) or as an isolated phenotypic effect (e.g. X-linked cleft palate; non-syndromic, autosomal dominant orofacial clefting). Several studies have suggested that chromosome 6p is a candidate region for a locus involved in orofacial clefting. We have used YAC clones from contigs in 6p25-p23 to investigate three unrelated cases of cleft lip and palate coincident with chromosome 6p abnormalities. Case 1 has bilateral cleft lip and palate and a balanced translocation reported as 46,XY,t(6,7)(p23;q36.1). Case 2 has multiple abnormalities including cleft lip and palate and was reported as 46,XX,del(6)(p23;pter). Case 3 has bilateral cleft lip and palate and carries a balanced translocation reported as 46,XX,t(6;9)(p23;q22.3). We have identified two YAC clones, both of which cross the breakpoint in cases 1 and 3 and are deleted in case 2. These clones map to 6p24.3 and therefore suggest the presence of a locus for orofacial clefting in this region. The HGP22 and AP2 genes, potentially involved in face formation, have been found to flank this region, while F13A maps further telomeric in 6p24.3/25.

  2. Comparative analysis of chicken chromosome 28 provides new clues to the evolutionary fragility of gene-rich vertebrate regions.

    Science.gov (United States)

    Gordon, Laurie; Yang, Shan; Tran-Gyamfi, Mary; Baggott, Dan; Christensen, Mari; Hamilton, Aaron; Crooijmans, Richard; Groenen, Martien; Lucas, Susan; Ovcharenko, Ivan; Stubbs, Lisa

    2007-11-01

    The chicken genome draft sequence has provided a valuable resource for studies of an important agricultural and experimental model species and an important data set for comparative analysis. However, some of the most gene-rich segments are missing from chicken genome draft assemblies, limiting the analysis of a substantial number of genes and preventing a closer look at regions that are especially prone to syntenic rearrangements. To facilitate the functional and evolutionary analysis of one especially gene-rich, rearrangement-prone genomic region, we analyzed sequence from BAC clones spanning chicken microchromosome GGA28; as a complement we also analyzed a gene-sparse, stable region from GGA11. In these two regions we documented the conservation and lineage-specific gain and loss of protein-coding genes and precisely mapped the locations of 31 major human-chicken syntenic breakpoints. Altogether, we identified 72 lineage-specific genes, many of which are found at or near syntenic breaks, implicating evolutionary breakpoint regions as major sites of genetic innovation and change. Twenty-two of the 31 breakpoint regions have been reused repeatedly as rearrangement breakpoints in vertebrate evolution. Compared with stable GC-matched regions, GGA28 is highly enriched in CpG islands, as are break-prone intervals identified elsewhere in the chicken genome; evolutionary breakpoints are further enriched in GC content and CpG islands, highlighting a potential role for these features in genome instability. These data support the hypothesis that chromosome rearrangements have not occurred randomly over the course of vertebrate evolution but are focused preferentially within "fragile" regions with unusual DNA sequence characteristics.

  3. A Narrow Segment of Maternal Uniparental Disomy of Chromosome 7q31-qter in Silver-Russell Syndrome Delimits a Candidate Gene Region

    Science.gov (United States)

    Hannula, Katariina; Lipsanen-Nyman, Marita; Kontiokari, Tero; Kere, Juha

    2001-01-01

    Maternal uniparental disomy of chromosome 7 (matUPD7), the inheritance of both chromosomes from only the mother, is observed in ∼10% of patients with Silver-Russell syndrome (SRS). It has been suggested that at least one imprinted gene that regulates growth and development resides on human chromosome 7. To date, three imprinted genes—PEG1/MEST, γ2-COP, and GRB10—have been identified on chromosome 7, but their role in the etiology of SRS remains uncertain. In a systematic screening with microsatellite markers, for matUPD7 cases among patients with SRS, we identified a patient who had a small segment of matUPD7 and biparental inheritance of the remainder of chromosome 7. Such a pattern may be explained by somatic recombination in the zygote. The matUPD7 segment at 7q31-qter extends for 35 Mb and includes the imprinted gene cluster of PEG1/MEST and γ2-COP at 7q32. GRB10 at 7p11.2-p12 is located within a region of biparental inheritance. Although partial UPD has previously been reported for chromosomes 6, 11, 14, and 15, this is the first report of a patient with SRS who has segmental matUPD7. Our findings delimit a candidate imprinted region sufficient to cause SRS. PMID:11112662

  4. Analysis of t(9;17)(q33.2;q25.3) chromosomal breakpoint regions and genetic association reveals novel candidate genes for bipolar disorder

    DEFF Research Database (Denmark)

    Rajkumar, A.P.; Christensen, Jane H.; Mattheisen, Manuel

    2015-01-01

    OBJECTIVES: Breakpoints of chromosomal abnormalities facilitate identification of novel candidate genes for psychiatric disorders. Genome-wide significant evidence supports the linkage between chromosome 17q25.3 and bipolar disorder (BD). Co-segregation of translocation t(9;17)(q33.2;q25.......3) with psychiatric disorders has been reported. We aimed to narrow down these chromosomal breakpoint regions and to investigate the associations between single nucleotide polymorphisms within these regions and BD as well as schizophrenia (SZ) in large genome-wide association study samples. METHODS: We cross......,856) data. Genetic associations between these disorders and single nucleotide polymorphisms within these breakpoint regions were analysed by BioQ, FORGE, and RegulomeDB programmes. RESULTS: Four protein-coding genes [coding for (endonuclease V (ENDOV), neuronal pentraxin I (NPTX1), ring finger protein 213...

  5. Association of gene polymorphisms in ABO blood group chromosomal regions and menstrual disorders.

    Science.gov (United States)

    Su, Yong; Kong, Gui-Lian; Su, Ya-Li; Zhou, Yan; Lv, Li-Fang; Wang, Qiong; Huang, Bao-Ping; Zheng, Rui-Zhi; Li, Quan-Zhong; Yuan, Hui-Juan; Zhao, Zhi-Gang

    2015-06-01

    This study aimed to investigate whether single nucleotide polymorphisms (SNPs) located near the gene of the ABO blood group play an important role in the genetic aetiology of menstrual disorders (MDs). Polymerase chain reaction-ligase detection reaction technology was used to detect eight SNPs near the ABO gene location on the chromosomes in 250 cases of MD and 250 cases of normal menstruation. The differences in the distribution of each genotype, as well as the allele frequency in the normal and control groups, were analysed using Pearson's χ(2) test to search for disease-associated loci. SHEsis software was used to analyse the linkage disequilibrium and haplotype frequencies and to inspect the correlation between haplotypes and the disease. Compared with the control group, the experimental group exhibited statistically significant differences in the genotype distribution frequencies of the rs657152 locus of the ABO blood group gene and the rs17250673 locus of the tumour necrosis factor cofactor 2 (TRAF2) gene, which is located downstream of the ABO gene. The allele distribution frequencies of rs657152 and rs495828 loci in the ABO blood group gene exhibited significant differences between the groups. Dominant and recessive genetic model analysis of each locus revealed that the experimental group exhibited statistically significant differences from the control group in the genotype distribution frequencies of rs657152 and rs495828 loci, respectively. These results indicate that the ABO blood group gene and TRAF2 gene may be a cause of MDs.

  6. Identification and uniparental expression of a novel gene from the Prader-Willi region of chromosome 15

    Energy Technology Data Exchange (ETDEWEB)

    Wevrick, R.; Kerns, J.A.; Francke, U. [Stanford Univ., CA (United States)

    1994-09-01

    The Prader-Willi syndrome (PWS) is a neurobehavioral disorder which occurs at a frequency of about 1/25,000. Most patients ({approximately}70%) have a cytogentic deletion of their paternal 15q11-q13 region, while {approximately}30% have uniparental maternal disomy. The parent of origin dependence of the phenotype is thought to be reflective of the uniparental pattern of expression of genes in the region, a phenomenon known as genomic imprinting. A small subset of PWS patient with a typical cytogenetic rearrangements has defined a critical region for genes involved in PWS. We have used STSs from the region to construct a YAC contig including the entire PWS critical region, which is about 350 kb considering presently characterized deletions. We are now using these YACs to isolate and characterize novel genes potentially involved in PWS. Overlapping YACs from the critical region were subjected to the technique of cDNA selection. Gel-purified YAC DNA was biotinylated during PCR amplification and annealed in solution to amplified cDNA. cDNAs remaining after hybridization washing, and denaturation of the hybrids were tested for localization within the YAC contig. One such cDNA mapped back to the YAC contig and was further analyzed. A full length cDNA clone was isolated from a fetal brain library and sequenced. The pattern of expression was determined in cell lines derived from Prader-Willi and Angelman patients and in normal individuals. The gene was found to have monoallelic, paternal expression in normal individuals and is marginally or not expressed in cell lines derived form Prader-Willi individuals. Expression in cell lines from Angelman patients, who are deleted for the same region on the maternal chromosome 15, was normal. Thus this apparently maternally imprinted gene is a candidate for involvement in the Prader-Willi phenotype.

  7. An autosomal recessive syndrome of severe mental retardation, cataract, coloboma and kyphosis maps to the pericentromeric region of chromosome 4.

    Science.gov (United States)

    Kahrizi, Kimia; Najmabadi, Hossein; Kariminejad, Roxana; Jamali, Payman; Malekpour, Mahdi; Garshasbi, Masoud; Ropers, Hans Hilger; Kuss, Andreas Walter; Tzschach, Andreas

    2009-01-01

    We report on three siblings with a novel mental retardation (MR) syndrome who were born to distantly related Iranian parents. The clinical problems comprised severe MR, cataracts with onset in late adolescence, kyphosis, contractures of large joints, bulbous nose with broad nasal bridge, and thick lips. Two patients also had uni- or bilateral iris coloboma. Linkage analysis revealed a single 10.4 Mb interval of homozygosity with significant LOD score in the pericentromeric region of chromosome 4 flanked by SNPs rs728293 (4p12) and rs1105434 (4q12). This interval contains more than 40 genes, none of which has been implicated in MR so far. The identification of the causative gene defect for this syndrome will provide new insights into the development of the brain and the eye.

  8. De novo LINE-1 retrotransposition in HepG2 cells preferentially targets gene poor regions of chromosome 13.

    Science.gov (United States)

    Bojang, Pasano; Anderton, Mark J; Roberts, Ruth A; Ramos, Kenneth S

    2014-08-01

    Long interspersed nuclear elements (Line-1 or L1s) account for ~17% of the human genome. While the majority of human L1s are inactive, ~80-100 elements remain retrotransposition competent and mobilize through RNA intermediates to different locations within the genome. De novo insertions of L1s account for polymorphic variation of the human genome and disruption of target loci at their new location. In the present study, fluorescence in situ hybridization and DNA sequencing were used to characterize retrotransposition profiles of L1(RP) in cultured human HepG2 cells. While expression of synthetic L1(RP) was associated with full-length and truncated insertions throughout the entire genome, a strong preference for gene-poor regions, such as those found in chromosome 13 was observed for full-length insertions. These findings shed light into L1 targeting mechanisms within the human genome and question the putative randomness of L1 retrotransposition.

  9. Genetic Dissection of the AZF Regions of the Human Y Chromosome: Thriller or Filler for Male (Infertility?

    Directory of Open Access Journals (Sweden)

    Paulo Navarro-Costa

    2010-01-01

    Full Text Available The azoospermia factor (AZF regions consist of three genetic domains in the long arm of the human Y chromosome referred to as AZFa, AZFb and AZFc. These are of importance for male fertility since they are home to genes required for spermatogenesis. In this paper a comprehensive analysis of AZF structure and gene content will be undertaken. Particular care will be given to the molecular mechanisms underlying the spermatogenic impairment phenotypes associated to AZF deletions. Analysis of the 14 different AZF genes or gene families argues for the existence of functional asymmetries between the determinants; while some are prominent players in spermatogenesis, others seem to modulate more subtly the program. In this regard, evidence supporting the notion that DDX3Y, KDM5D, RBMY1A1, DAZ, and CDY represent key AZF spermatogenic determinants will be discussed.

  10. Genetic linkage mapping of the dehydroepiandrosterone sulfotransferase (STD) gene on the chromosome 19q13.3 region

    Energy Technology Data Exchange (ETDEWEB)

    Durocher, F.; Morissette, J.; Dufort, I.; Simard, J.; Luu-The, V. [Laval Univ. Quebec (Canada)

    1995-10-10

    In the human liver and adrenal, there is a single hydroxysteroid sulfotransferase, which catalyzes the transformation of dehydroepiandrosterone to dehydroepiandrosterone sulfate, the most abundantly circulating steroid in humans, and also catalyzes the sulfation of a series of other 3{beta}-hydroxysteroids as well as cholesterol. Dehydroepiandrosterone sulfate serves as precursor for the formation of active androgens and estrogens in several peripheral tissues, indicating that hydroxysteroid sulfotransferase plays a pivotal role in controlling the hormonal action of sex steroids by regulating their bioavailability. We recently elucidated the structure of the gene encoding hydroxysteroid sulfotransferase (STD), also designated dehydroepiandrosterone sulfotransferase, which spans 17 kb and contains six exons. The STD gene was preliminarily assigned to chromosome 19 by polymerase chain reaction (PCR) amplification of DNA from a panel of human/rodent somatic cell hybrids. To locate the STD gene, the novel biallelic polymorphism found in intron 2 was genotyped in eight CEPH reference families by direct sequencing of PCR products. Two-point linkage analysis was first performed between the latter polymorphism and chromosome 19 markers from Genethon and NIH/CEPH. The closest linkage was observed with D19S412 (Z{sub max} = 9.23; {theta}{sub max} 0.038) and HRC (Z{sub max} =5.95; {theta}{sub max}0.036), located on the 19q13.3 region. A framework map including six Genethon markers flanking the polymorphic STD gene was created by multipoint linkage analysis. Thereafter, a high-resolution genetic map of the region was constructed, yielding to the following order: qter-D19S414-D19S224-D19S420-D19S217-(APOC2-D19S412)-(STD-HRC)-KLK-D19S22-D19S180-PRKCG-D19S418-tel. 24 refs., 2 figs.

  11. Gene-rich chromosomal regions are preferentially localized in the lamin B deficient nuclear blebs of atypical progeria cells.

    Science.gov (United States)

    Bercht Pfleghaar, Katrin; Taimen, Pekka; Butin-Israeli, Veronika; Shimi, Takeshi; Langer-Freitag, Sabine; Markaki, Yolanda; Goldman, Anne E; Wehnert, Manfred; Goldman, Robert D

    2015-01-01

    More than 20 mutations in the gene encoding A-type lamins (LMNA) cause progeria, a rare premature aging disorder. The major pathognomonic hallmarks of progeria cells are seen as nuclear deformations or blebs that are related to the redistribution of A- and B-type lamins within the nuclear lamina. However, the functional significance of these progeria-associated blebs remains unknown. We have carried out an analysis of the structural and functional consequences of progeria-associated nuclear blebs in dermal fibroblasts from a progeria patient carrying a rare point mutation p.S143F (C428T) in lamin A/C. These blebs form microdomains that are devoid of major structural components of the nuclear envelope (NE)/lamina including B-type lamins and nuclear pore complexes (NPCs) and are enriched in A-type lamins. Using laser capture microdissection and comparative genomic hybridization (CGH) analyses, we show that, while these domains are devoid of centromeric heterochromatin and gene-poor regions of chromosomes, they are enriched in gene-rich chromosomal regions. The active form of RNA polymerase II is also greatly enriched in blebs as well as nascent RNA but the nuclear co-activator SKIP is significantly reduced in blebs compared to other transcription factors. Our results suggest that the p.S143F progeria mutation has a severe impact not only on the structure of the lamina but also on the organization of interphase chromatin domains and transcription. These structural defects are likely to contribute to gene expression changes reported in progeria and other types of laminopathies.

  12. Four out of eight genes in a mouse chromosome 7 congenic donor region are candidate obesity genes

    Science.gov (United States)

    Sarahan, Kari A.; Fisler, Janis S.

    2011-01-01

    We previously identified a region of mouse chromosome 7 that influences body fat mass in F2 littermates of congenic × background intercrosses. Current analyses revealed that alleles in the donor region of the subcongenic B6.C-D7Mit318 (318) promoted a twofold increase in adiposity in homozygous lines of 318 compared with background C57BL/6ByJ (B6By) mice. Parent-of-origin effects were discounted through cross-fostering studies and an F1 reciprocal cross. Mapping of the donor region revealed that it has a maximal size of 2.8 Mb (minimum 1.8 Mb) and contains a maximum of eight protein coding genes. Quantitative PCR in whole brain, liver, and gonadal white adipose tissue (GWAT) revealed differential expression between genotypes for three genes in females and two genes in males. Alpha-2,8-sialyltransferase 8B (St8sia2) showed reduced 318 mRNA levels in brain for females and males and in GWAT for females only. Both sexes of 318 mice had reduced Repulsive guidance molecule-a (Rgma) expression in GWAT. In brain, Family with sequence similarity 174 member b (Fam174b) had increased expression in 318 females, whereas Chromodomain helicase DNA binding protein 2 (Chd2-2) had reduced expression in 318 males. No donor region genes were differentially expressed in liver. Sequence analysis of coding exons for all genes in the 318 donor region revealed only one single nucleotide polymorphism that produced a nonsynonymous missense mutation, Gln7Pro, in Fam174b. Our findings highlight the difficulty of using expression and sequence to identify quantitative trait genes underlying obesity even in small genomic regions. PMID:21730028

  13. Four out of eight genes in a mouse chromosome 7 congenic donor region are candidate obesity genes.

    Science.gov (United States)

    Sarahan, Kari A; Fisler, Janis S; Warden, Craig H

    2011-09-22

    We previously identified a region of mouse chromosome 7 that influences body fat mass in F2 littermates of congenic × background intercrosses. Current analyses revealed that alleles in the donor region of the subcongenic B6.C-D7Mit318 (318) promoted a twofold increase in adiposity in homozygous lines of 318 compared with background C57BL/6ByJ (B6By) mice. Parent-of-origin effects were discounted through cross-fostering studies and an F1 reciprocal cross. Mapping of the donor region revealed that it has a maximal size of 2.8 Mb (minimum 1.8 Mb) and contains a maximum of eight protein coding genes. Quantitative PCR in whole brain, liver, and gonadal white adipose tissue (GWAT) revealed differential expression between genotypes for three genes in females and two genes in males. Alpha-2,8-sialyltransferase 8B (St8sia2) showed reduced 318 mRNA levels in brain for females and males and in GWAT for females only. Both sexes of 318 mice had reduced Repulsive guidance molecule-a (Rgma) expression in GWAT. In brain, Family with sequence similarity 174 member b (Fam174b) had increased expression in 318 females, whereas Chromodomain helicase DNA binding protein 2 (Chd2-2) had reduced expression in 318 males. No donor region genes were differentially expressed in liver. Sequence analysis of coding exons for all genes in the 318 donor region revealed only one single nucleotide polymorphism that produced a nonsynonymous missense mutation, Gln7Pro, in Fam174b. Our findings highlight the difficulty of using expression and sequence to identify quantitative trait genes underlying obesity even in small genomic regions.

  14. Pasture names with Romance and Slavic roots facilitate dissection of Y chromosome variation in an exclusively German-speaking alpine region.

    Directory of Open Access Journals (Sweden)

    Harald Niederstätter

    Full Text Available The small alpine district of East Tyrol (Austria has an exceptional demographic history. It was contemporaneously inhabited by members of the Romance, the Slavic and the Germanic language groups for centuries. Since the Late Middle Ages, however, the population of the principally agrarian-oriented area is solely Germanic speaking. Historic facts about East Tyrol's colonization are rare, but spatial density-distribution analysis based on the etymology of place-names has facilitated accurate spatial mapping of the various language groups' former settlement regions. To test for present-day Y chromosome population substructure, molecular genetic data were compared to the information attained by the linguistic analysis of pasture names. The linguistic data were used for subdividing East Tyrol into two regions of former Romance (A and Slavic (B settlement. Samples from 270 East Tyrolean men were genotyped for 17 Y-chromosomal microsatellites (Y-STRs and 27 single nucleotide polymorphisms (Y-SNPs. Analysis of the probands' surnames revealed no evidence for spatial genetic structuring. Also, spatial autocorrelation analysis did not indicate significant correlation between genetic (Y-STR haplotypes and geographic distance. Haplogroup R-M17 chromosomes, however, were absent in region A, but constituted one of the most frequent haplogroups in region B. The R-M343 (R1b clade showed a marked and complementary frequency distribution pattern in these two regions. To further test East Tyrol's modern Y-chromosomal landscape for geographic patterning attributable to the early history of settlement in this alpine area, principal coordinates analysis was performed. The Y-STR haplotypes from region A clearly clustered with those of Romance reference populations and the samples from region B matched best with Germanic speaking reference populations. The combined use of onomastic and molecular genetic data revealed and mapped the marked structuring of the distribution

  15. Pasture Names with Romance and Slavic Roots Facilitate Dissection of Y Chromosome Variation in an Exclusively German-Speaking Alpine Region

    Science.gov (United States)

    Niederstätter, Harald; Rampl, Gerhard; Erhart, Daniel; Pitterl, Florian; Oberacher, Herbert; Neuhuber, Franz; Hausner, Isolde; Gassner, Christoph; Schennach, Harald; Berger, Burkhard; Parson, Walther

    2012-01-01

    The small alpine district of East Tyrol (Austria) has an exceptional demographic history. It was contemporaneously inhabited by members of the Romance, the Slavic and the Germanic language groups for centuries. Since the Late Middle Ages, however, the population of the principally agrarian-oriented area is solely Germanic speaking. Historic facts about East Tyrol's colonization are rare, but spatial density-distribution analysis based on the etymology of place-names has facilitated accurate spatial mapping of the various language groups' former settlement regions. To test for present-day Y chromosome population substructure, molecular genetic data were compared to the information attained by the linguistic analysis of pasture names. The linguistic data were used for subdividing East Tyrol into two regions of former Romance (A) and Slavic (B) settlement. Samples from 270 East Tyrolean men were genotyped for 17 Y-chromosomal microsatellites (Y-STRs) and 27 single nucleotide polymorphisms (Y-SNPs). Analysis of the probands' surnames revealed no evidence for spatial genetic structuring. Also, spatial autocorrelation analysis did not indicate significant correlation between genetic (Y-STR haplotypes) and geographic distance. Haplogroup R-M17 chromosomes, however, were absent in region A, but constituted one of the most frequent haplogroups in region B. The R-M343 (R1b) clade showed a marked and complementary frequency distribution pattern in these two regions. To further test East Tyrol's modern Y-chromosomal landscape for geographic patterning attributable to the early history of settlement in this alpine area, principal coordinates analysis was performed. The Y-STR haplotypes from region A clearly clustered with those of Romance reference populations and the samples from region B matched best with Germanic speaking reference populations. The combined use of onomastic and molecular genetic data revealed and mapped the marked structuring of the distribution of Y

  16. Pasture names with Romance and Slavic roots facilitate dissection of Y chromosome variation in an exclusively German-speaking alpine region.

    Science.gov (United States)

    Niederstätter, Harald; Rampl, Gerhard; Erhart, Daniel; Pitterl, Florian; Oberacher, Herbert; Neuhuber, Franz; Hausner, Isolde; Gassner, Christoph; Schennach, Harald; Berger, Burkhard; Parson, Walther

    2012-01-01

    The small alpine district of East Tyrol (Austria) has an exceptional demographic history. It was contemporaneously inhabited by members of the Romance, the Slavic and the Germanic language groups for centuries. Since the Late Middle Ages, however, the population of the principally agrarian-oriented area is solely Germanic speaking. Historic facts about East Tyrol's colonization are rare, but spatial density-distribution analysis based on the etymology of place-names has facilitated accurate spatial mapping of the various language groups' former settlement regions. To test for present-day Y chromosome population substructure, molecular genetic data were compared to the information attained by the linguistic analysis of pasture names. The linguistic data were used for subdividing East Tyrol into two regions of former Romance (A) and Slavic (B) settlement. Samples from 270 East Tyrolean men were genotyped for 17 Y-chromosomal microsatellites (Y-STRs) and 27 single nucleotide polymorphisms (Y-SNPs). Analysis of the probands' surnames revealed no evidence for spatial genetic structuring. Also, spatial autocorrelation analysis did not indicate significant correlation between genetic (Y-STR haplotypes) and geographic distance. Haplogroup R-M17 chromosomes, however, were absent in region A, but constituted one of the most frequent haplogroups in region B. The R-M343 (R1b) clade showed a marked and complementary frequency distribution pattern in these two regions. To further test East Tyrol's modern Y-chromosomal landscape for geographic patterning attributable to the early history of settlement in this alpine area, principal coordinates analysis was performed. The Y-STR haplotypes from region A clearly clustered with those of Romance reference populations and the samples from region B matched best with Germanic speaking reference populations. The combined use of onomastic and molecular genetic data revealed and mapped the marked structuring of the distribution of Y

  17. Control regions for chromosome replication are conserved with respect to both sequence and location between Escherichia coli strains

    DEFF Research Database (Denmark)

    Frimodt-Møller, Jakob; Charbon, Godefroid; Krogfelt, Karen Angeliki;

    2015-01-01

    In Escherichia coli, chromosome replication is initiated from oriC by the DnaA initiator protein associated with ATP. Three non-coding regions contribute to the activity of DnaA. The datA locus is instrumental in conversion of DnaAATP to DnaAADP (DDAH; datA dependent DnaAATP hydrolysis) whereas Dna......A rejuvenation sequences 1 and 2 (DARS1 and DARS2) reactivate DnaAADP to DnaAATP. The structural organization of oriC, datA, DARS1 and DARS2 were found conserved between 59 fully sequenced E. coli genomes, with differences primarily in the non-functional spacer regions between key protein binding sites....... Competition experiments during balanced growth in rich medium and during mouse colonization indicated roles of datA, DARS1 and DARS2 for bacterial fitness although the relative contribution of each region differed between growth conditions. We suggest that this fitness cost contribute to conservation of both...

  18. Y chromosome in Turner syndrome: detection of hidden mosaicism and the report of a rare X;Y translocation case.

    Science.gov (United States)

    Bispo, Adriana Valéria Sales; Burégio-Frota, Pollyanna; Oliveira dos Santos, Luana; Leal, Gabriela Ferraz; Duarte, Andrea Rezende; Araújo, Jacqueline; Cavalcante da Silva, Vanessa; Muniz, Maria Tereza Cartaxo; Liehr, Thomas; Santos, Neide

    2014-10-01

    Turner syndrome (TS) is a common genetic disorder in females associated with the absence of complete or parts of a second sex chromosome. In 5-12% of patients, mosaicism for a cell line with a normal or structurally abnormal Y chromosome is identified. The presence of Y-chromosome material is of medical importance because it results in an increased risk of developing gonadal tumours and virilisation. Molecular study and fluorescence in situ hybridisation approaches were used to study 74 Brazilian TS patients in order to determine the frequency of hidden Y-chromosome mosaicism, and to infer the potential risk of developing malignancies. Additionally, we describe one TS girl with a very uncommon karyotype 46,X,der(X)t(X;Y)(p22.3?2;q11.23) comprising a partial monosomy of Xp22.3?2 together with a partial monosomy of Yq11.23. The presence of cryptic Y-chromosome-specific sequences was detected in 2.7% of the cases. All patients with Y-chromosome-positive sequences showed normal female genitalia with no signs of virilisation. Indeed, the clinical data from Y-chromosome-positive patients was very similar to those with Y-negative results. Therefore, we recommend that the search for hidden Y-chromosome mosaicism should be carried out in all TS cases and not be limited to virilised patients or carriers of a specific karyotype.

  19. Allele and haplotype diversity of X-chromosomal STRs in Ivory Coast.

    Science.gov (United States)

    Pasino, Serena; Caratti, Stefano; Del Pero, Massimiliano; Santovito, Alfredo; Torre, Carlo; Robino, Carlo

    2011-09-01

    Twenty-one X-chromosomal short tandem repeat (STR) loci, including the six clusters of linked markers DXS10148-DXS10135-DXS8378 (Xp22), DXS7132-DXS10079-DXS10074 (Xq12), DXS6801-DXS6809-DXS6789 (Xq21), DXS7424-DXS101 (Xq22), DXS10103-HPRTB-DXS10101 (Xq26), DXS8377-DXS10146-DXS10134-DXS7423 (Xq28) and the loci DXS6800, GATA172D05 and DXS10011 were typed in a population sample from Ivory Coast (n=125; 51 men and 74 women). Allele and haplotype frequencies as well as linkage disequilibrium data for kinship calculations are provided. On the whole, no significant differences in the genetic variability of X-STR markers were observed between Ivorians and other sub-Saharan African populations belonging to the Niger-Kordofanian linguistic group.

  20. Subnuclear relocalization and silencing of a chromosomal region by an ectopic ribosomal DNA repeat

    DEFF Research Database (Denmark)

    Jakociunas, Tadas; Domange Jordö, Marie Elise; Mebarek, Mazhoura Aït;

    2013-01-01

    dimerization, providing a mechanism for the observed relocalization. Replacing the full rDNA repeat with Reb1-binding sites, and using mutants lacking the histone H3K9 methyltransferase Clr4, indicated that the relocalized region was silenced redundantly by heterochromatin and another mechanism, plausibly...

  1. A variant of the H6 homeobox gene maps to the 10q25.1-q26.2 region of human chromosome 10

    Energy Technology Data Exchange (ETDEWEB)

    Stadler, H.S.; Solursh, M. [Univ. of Iowa, Iowa City, IA (United States); Goodfellow, P.J. [Washington Univ. School of Medicine, St. Louis, MO (United States)] [and others

    1994-09-01

    Homeobox genes represent a class of transcription factors which play a major role in the regulation of embryogenesis. Utilizing primers based on the conserved regions of the H6 homeobox gene, we were able to amplify several H6-like homeobox sequences from human genomic DNA. Analysis of these sequences indicated that at least 3 distinct H6-like homeobox regions may be present in Homo sapiens. From these distinct homeobox regions, primers were selected to screen a CEPH mega-YAC library for genomic clones containing the variant H6-like sequences. These screenings identified a YAC clone (YH6var) which contained the variant H6-like homeobox sequence. Utilizing a human/rodent somatic cell panel (Coriell B), the end clones from YH6var were chromosomally mapped to human chromosomes 10 and 16, indicating that YH6var was chimeric. An additional sequence flanking the H6 variant homeobox region was derived by inverse-PCR using YH6var as a template. From this flanking sequence, Homo sapien-specific primers were selected to assign the H6 variant to human chromosome 10 using the same Coriell B panel. The H6 variant gene was sublocalized to the 10q25.1-q26.2 region using a panel of somatic cell hybrids that retain well-characterized deletions/derivatives of chromosome 10. We are currently screening for STS-based markers for genetic linkage studies to confirm our physical mapping to the 10q25.1-q26.2 region as well as for use in linkage studies with developmental defects mapping to the same chromosomal region.

  2. Characterization of the hemA-prs region of the Escherichia coli and Salmonella typhimurium chromosomes

    DEFF Research Database (Denmark)

    Post, David A.; Hove-Jensen, Bjarne; Switzer, Robert L.

    1993-01-01

    The prs gene, encoding phosphoribosylpyrophosphate synthetase, is preceded by a leader, which is 302 bp long in Escherichia coli and 417 bp in Salmonella typhimurium. A potential open reading frame (ORF) extends across the prs promoter and into the leader. The region between the prs coding region...... direction as the prs gene with ORF 2 extending into the prs leader. Northern blot analysis showed that the prs message in E. coli was on 1.3 and 2.7 kb transcripts. The shorter transcript encoded the prs gene only, while the longer transcript also encoded the two ORFs. Thus, the prs gene is transcribed from...... two promoters, the first promoter (P1) originating upstream of ORF 1, and expressing the prs gene in a tricistronic operon and a second promoter (P2), located within the ORF 2 coding frame, which transcribes the prs gene only. The transcripts encoding prs only were 20 times as abundant...

  3. Narrowing the Duane syndrome critical region at chromosome 8q13 down to 40 kb.

    Science.gov (United States)

    Calabrese, G; Telvi, L; Capodiferro, F; Morizio, E; Pizzuti, A; Stuppia, L; Bordoni, R; Ion, A; Fantasia, D; Mingarelli, R; Palka, G

    2000-05-01

    Duane syndrome (MIM 126800) is an autosomal dominant disorder characterised by primary strabismus and other ocular anomalies, associated with variable deficiency of binocular sight. We have recently identified a syndrome carrying a reciprocal translation t(6;8)(q26;q13). FISH and PCR analyses using a YAC contig spanning the SRO narrowed the Duane region to a < 1 cM interval between markers SHGC37325 and W14901. In addition, the identification and mapping of two PAC clones flanking the translocation breakpoint, allowed us to further narrow the critical region to about 40 kb. As part of these mapping studies, we have also refined the map position of AMYB, a putative candidate gene, to 8q13, centromeric to Duane locus. AMYB is expressed in brain cortex and genital crests and has been previously mapped to 8q22.

  4. Characterization of the genomic organization of the region bordering the centromere of chromosome V of Podospora anserina by direct sequencing.

    Science.gov (United States)

    Silar, Philippe; Barreau, Christian; Debuchy, Robert; Kicka, Sébastien; Turcq, Béatrice; Sainsard-Chanet, Annie; Sellem, Carole H; Billault, Alain; Cattolico, Laurence; Duprat, Simone; Weissenbach, Jean

    2003-08-01

    A Podospora anserina BAC library of 4800 clones has been constructed in the vector pBHYG allowing direct selection in fungi. Screening of the BAC collection for centromeric sequences of chromosome V allowed the recovery of clones localized on either sides of the centromere, but no BAC clone was found to contain the centromere. Seven BAC clones containing 322,195 and 156,244bp from either sides of the centromeric region were sequenced and annotated. One 5S rRNA gene, 5 tRNA genes, and 163 putative coding sequences (CDS) were identified. Among these, only six CDS seem specific to P. anserina. The gene density in the centromeric region is approximately one gene every 2.8kb. Extrapolation of this gene density to the whole genome of P. anserina suggests that the genome contains about 11,000 genes. Synteny analyses between P. anserina and Neurospora crassa show that co-linearity extends at the most to a few genes, suggesting rapid genome rearrangements between these two species.

  5. Copy-number variations in Y-chromosomal azoospermia factor regions identified by multiplex ligation-dependent probe amplification.

    Science.gov (United States)

    Saito, Kazuki; Miyado, Mami; Kobori, Yoshitomo; Tanaka, Yoko; Ishikawa, Hiromichi; Yoshida, Atsumi; Katsumi, Momori; Saito, Hidekazu; Kubota, Toshiro; Okada, Hiroshi; Ogata, Tsutomu; Fukami, Maki

    2015-03-01

    Although copy-number variations (CNVs) in Y-chromosomal azoospermia factor (AZF) regions have been associated with the risk of spermatogenic failure (SF), the precise frequency, genomic basis and clinical consequences of these CNVs remain unclear. Here we performed multiplex ligation-dependent probe amplification (MLPA) analysis of 56 Japanese SF patients and 65 control individuals. We compared the results of MLPA with those of conventional sequence-tagged site PCR analyses. Eleven simple and complex CNVs, including three hitherto unreported variations, were identified by MLPA. Seven of the 11 CNVs were undetectable by conventional analyses. CNVs were widely distributed in AZF regions and shared by ~60% of the patients and ~40% of the controls. Most breakpoints resided within locus-specific repeats. The majority of CNVs, including the most common gr/gr deletion, were identified in the patient and control groups at similar frequencies, whereas simple duplications were observed exclusively in the patient group. The results imply that AZF-linked CNVs are more frequent and heterogeneous than previously reported. Non-allelic homologous recombination likely underlies these CNVs. Our data confirm the functional neutrality of the gr/gr deletion in the Japanese population. We also found a possible association between AZF-linked simple duplications and SF, which needs to be evaluated in future studies.

  6. Quantitative variation in obesity-related traits and insulin precursors linked to the OB gene region on human chromosome 7

    Energy Technology Data Exchange (ETDEWEB)

    Duggirala, R.; Stern, M.P.; Reinhart, L.J. [Univ. of Texas Health Science Center, San Antonio, TX (United States)] [and others

    1996-09-01

    Despite the evidence that human obesity has strong genetic determinants, efforts at identifying specific genes that influence human obesity have largely been unsuccessful. Using the sibship data obtained from 32 low-income Mexican American pedigrees ascertained on a type II diabetic proband and a multipoint variance-components method, we tested for linkage between various obesity-related traits plus associated metabolic traits and 15 markers on human chromosome 7. We found evidence for linkage between markers in the OB gene region and various traits, as follows: D7S514 and extremity skinfolds (LOD = 3.1), human carboxypeptidase A1 (HCPA1) and 32,33-split proinsulin level (LOD = 4.2), and HCPA1 and proinsulin level (LOD = 3.2). A putative susceptibility locus linked to the marker D7S514 explained 56% of the total phenotypic variation in extremity skinfolds. Variation at the HCPA1 locus explained 64% of phenotypic variation in proinsulin level and {approximately}73% of phenotypic variation in split proinsulin concentration, respectively. Weaker evidence for linkage to several other obesity-related traits (e.g., waist circumference, body-mass index, fat mass by bioimpedance, etc.) was observed for a genetic location, which is {approximately}15 cM telomeric to OB. In conclusion, our study reveals that the OB region plays a significant role in determining the phenotypic variation of both insulin precursors and obesity-related traits, at least in Mexican Americans. 66 refs., 3 figs., 4 tabs.

  7. In silico prediction of structure and functions for some proteins of male-specific region of the human Y chromosome.

    Science.gov (United States)

    Saha, Chinmoy; Polash, Ahsan Habib; Islam, Md Tariqul; Shafrin, Farhana

    2013-12-01

    Male-specific region of the human Y chromosome (MSY) comprises 95% of its length that is functionally active. This portion inherits in block from father to male offspring. Most of the genes in the MSY region are involved in male-specific function, such as sex determination and spermatogenesis; also contains genes probably involved in other cellular functions. However, a detailed characterization of numerous MSY-encoded proteins still remains to be done. In this study, 12 uncharacterized proteins of MSY were analyzed through bioinformatics tools for structural and functional characterization. Within these 12 proteins, a total of 55 domains were found, with DnaJ domain signature corresponding to be the highest (11%) followed by both FAD-dependent pyridine nucleotide reductase signature and fumarate lyase superfamily signature (9%). The 3D structures of our selected proteins were built up using homology modeling and the protein threading approaches. These predicted structures confirmed in detail the stereochemistry; indicating reasonably good quality model. Furthermore the predicted functions and the proteins with whom they interact established their biological role and their mechanism of action at molecular level. The results of these structure-functional annotations provide a comprehensive view of the proteins encoded by MSY, which sheds light on their biological functions and molecular mechanisms. The data presented in this study may assist in future prognosis of several human diseases such as Turner syndrome, gonadal sex reversal, spermatogenic failure, and gonadoblastoma.

  8. Towards the cloning of imprinted genes in the Prader-Willi/Angelman region of chromosome 15q11-q13

    Energy Technology Data Exchange (ETDEWEB)

    Nakao, M.; Sutcliffe, J.S.; Beaudet, A.L. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-09-01

    Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct clinical phenotypes resulting from paternal and maternal deficiencies respectively in human chromosome 15q11-q13. The data suggest the presence of oppositely imprinted genes in the region, and the gene for small nuclear ribonucleoprotein-associated polypeptide N (SNRPN) has been identified as a candidate gene for PWS. Previous strategies for positional cloning identified a number of transcripts from the PWS/AS region, and two of them, PAR-5 (D15S226E) and PAR-1 (D15S227E), are paternally expressed in cultured human cells from patients deleted for 15q11-q13 as is SNRPN. Cosmid contig maps have been developed from the following YACs (contained loci in parentheses): 307A12 (D15S13), 457B4 (SNRPN), 132D4 (D15S10), A229A2, and 378A12 (D15S113), to facilitate molecular studies of PWS and AS. Exon trapping has been employed to isolate putative exons from these overlapping cosmids. Two trapped fragments from the D15S113 region and one fragment from the SNRPN region has been isolated. Sequence information is available for all of the fragments. In addition to imprinting analysis in cultured human cells, we have developed a method to detect imprinting in mouse and human using a GC-clamped denaturing gradient gel electrophoresis strategy, in combination with reverse transcription-polymerase chain reaction. The imprinting analyses of putative exons are in progress to investigate their possible candidacy for involvement in PWS or AS phenotypes.

  9. Positive selection in the chromosome 16 VKORC1 genomic region has contributed to the variability of anticoagulant response in humans.

    Directory of Open Access Journals (Sweden)

    Blandine Patillon

    Full Text Available VKORC1 (vitamin K epoxide reductase complex subunit 1, 16p11.2 is the main genetic determinant of human response to oral anticoagulants of antivitamin K type (AVK. This gene was recently suggested to be a putative target of positive selection in East Asian populations. In this study, we genotyped the HGDP-CEPH Panel for six VKORC1 SNPs and downloaded chromosome 16 genotypes from the HGDP-CEPH database in order to characterize the geographic distribution of footprints of positive selection within and around this locus. A unique VKORC1 haplotype carrying the promoter mutation associated with AVK sensitivity showed especially high frequencies in all the 17 HGDP-CEPH East Asian population samples. VKORC1 and 24 neighboring genes were found to lie in a 505 kb region of strong linkage disequilibrium in these populations. Patterns of allele frequency differentiation and haplotype structure suggest that this genomic region has been submitted to a near complete selective sweep in all East Asian populations and only in this geographic area. The most extreme scores of the different selection tests are found within a smaller 45 kb region that contains VKORC1 and three other genes (BCKDK, MYST1 (KAT8, and PRSS8 with different functions. Because of the strong linkage disequilibrium, it is not possible to determine if VKORC1 or one of the three other genes is the target of this strong positive selection that could explain present-day differences among human populations in AVK dose requirement. Our results show that the extended region surrounding a presumable single target of positive selection should be analyzed for genetic variation in a wide range of genetically diverse populations in order to account for other neighboring and confounding selective events and the hitchhiking effect.

  10. Positive selection in the chromosome 16 VKORC1 genomic region has contributed to the variability of anticoagulant response in humans.

    Science.gov (United States)

    Patillon, Blandine; Luisi, Pierre; Blanché, Hélène; Patin, Etienne; Cann, Howard M; Génin, Emmanuelle; Sabbagh, Audrey

    2012-01-01

    VKORC1 (vitamin K epoxide reductase complex subunit 1, 16p11.2) is the main genetic determinant of human response to oral anticoagulants of antivitamin K type (AVK). This gene was recently suggested to be a putative target of positive selection in East Asian populations. In this study, we genotyped the HGDP-CEPH Panel for six VKORC1 SNPs and downloaded chromosome 16 genotypes from the HGDP-CEPH database in order to characterize the geographic distribution of footprints of positive selection within and around this locus. A unique VKORC1 haplotype carrying the promoter mutation associated with AVK sensitivity showed especially high frequencies in all the 17 HGDP-CEPH East Asian population samples. VKORC1 and 24 neighboring genes were found to lie in a 505 kb region of strong linkage disequilibrium in these populations. Patterns of allele frequency differentiation and haplotype structure suggest that this genomic region has been submitted to a near complete selective sweep in all East Asian populations and only in this geographic area. The most extreme scores of the different selection tests are found within a smaller 45 kb region that contains VKORC1 and three other genes (BCKDK, MYST1 (KAT8), and PRSS8) with different functions. Because of the strong linkage disequilibrium, it is not possible to determine if VKORC1 or one of the three other genes is the target of this strong positive selection that could explain present-day differences among human populations in AVK dose requirement. Our results show that the extended region surrounding a presumable single target of positive selection should be analyzed for genetic variation in a wide range of genetically diverse populations in order to account for other neighboring and confounding selective events and the hitchhiking effect.

  11. Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk

    NARCIS (Netherlands)

    Wei-Yu Lin; N.J. Camp (Nicola); M. Ghoussaini (Maya); J. Beesley (Jonathan); K. Michailidou (Kyriaki); J. Hopper (John); C. Apicella (Carmel); M.C. Southey (Melissa); J. Stone (Jennifer); M.K. Schmidt (Marjanka); A. Broeks (Annegien); L.J. van 't Veer (Laura); E.J. Th Rutgers (Emiel J.); K.R. Muir (K.); A. Lophatananon (Artitaya); S. Stewart-Brown (Sarah); P. Siriwanarangsan (Pornthep); P.A. Fasching (Peter); L. Haeberle (Lothar); A.B. Ekici (Arif); M.W. Beckmann (Matthias W.); J. Peto (Julian); I. dos Santos Silva (Isabel); O. Fletcher (Olivia); N. Johnson (Nichola); M.K. Bolla (Manjeet); Q. Wang (Qing); J. Dennis (Joe); E.J. Sawyer (Elinor); T. Cheng (Timothy); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); Frederik Marmé; H. Surowy (Harald); B. Burwinkel (Barbara); P. Guénel (Pascal); T. Truong (Thérèse); F. Menegaux (Florence); C. Mulot (Claire); S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); S.F. Nielsen (Sune); H. Flyger (Henrik); J. Benítez (Javier); M.P. Zamora (Pilar); J.I.A. Perez (Jose Ignacio Arias); P. Menéndez (Primitiva); A. González-Neira (Anna); G. Pita (G.); M. Rosario Alonso; N. Álvarez (Nuria); D. Herrero (Daniel); H. Anton-Culver (Hoda); H. Brenner (Hermann); A.K. Dieffenbach (Aida Karina); V. Arndt (Volker); C. Stegmaier (Christa); A. Meindl (Alfons); P. Lichtner (Peter); R.K. Schmutzler (Rita); B. Müller-Myhsok (B.); H. Brauch (Hiltrud); T. Brüning (Thomas); Y.-D. Ko (Yon-Dschun); D.C. Tessier (Daniel C.); D. Vincent (Daniel); F. Bacot (Francois); H. Nevanlinna (Heli); K. Aittomäki (Kristiina); C. Blomqvist (Carl); S. Khan (Sofia); K. Matsuo (Keitaro); H. Ito (Hidemi); H. Iwata (Hisato); A. Horio (Akiyo); N.V. Bogdanova (Natalia); N.N. Antonenkova (Natalia); T. Dörk (Thilo); A. Lindblom (Annika); S. Margolin (Sara); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J.M. Hartikainen (J.); A.H. Wu (Anna H.); C.-C. Tseng (Chiu-chen); D. Van Den Berg (David); D.O. Stram (Daniel O.); P. Neven (Patrick); E. Wauters (Erwin); H. Wildiers (Hans); D. Lambrechts (Diether); J. Chang-Claude (Jenny); A. Rudolph (Anja); P. Seibold (Petra); D. Flesch-Janys (Dieter); P. Radice (Paolo); P. Peterlongo (Paolo); S. Manoukian (Siranoush); B. Bonnani (Bernardo); F.J. Couch (Fergus); X. Wang (Xianshu); C. Vachon (Celine); K. Purrington (Kristen); G.G. Giles (Graham G.); R.L. Milne (Roger L.); C.A. McLean (Catriona Ann); C.A. Haiman (Christopher); B.E. Henderson (Brian); F.R. Schumacher (Fredrick); L. Le Marchand (Loic); J. Simard (Jacques); M.S. Goldberg (Mark); F. Labrèche (France); M. Dumont (Martine); S.-H. Teo; C.H. Yip (Cheng Har); N. Hassan (Norhashimah); E.N. Vithana (Eranga); V. Kristensen (Vessela); W. Zheng (Wei); S.L. Deming-Halverson (Sandra); M. Shrubsole (Martha); J. Long (Jirong); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); S. Kauppila (Saila); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); S. Tchatchou (Sandrine); P. Devilee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); C.J. van Asperen (Christi); M. García-Closas (Montserrat); J.D. Figueroa (Jonine); J. Lissowska (Jolanta); L.A. Brinton (Louise); K. Czene (Kamila); H. Darabi (Hatef); M. Eriksson (Mikael); J.S. Brand (Judith S.); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); A.M.W. Van DenOuweland (Ans M.W.); A. Jager (Agnes); J. Li (Jingmei); J. Liu (Jianjun); M.K. Humphreys (Manjeet); X.-O. Shu (Xiao-Ou); W. Lu (Wei); Y. Gao; H. Cai (Hui); S.S. Cross (Simon); M.W.R. Reed (Malcolm); W.J. Blot (William); L.B. Signorello (Lisa B.); Q. Cai (Qiuyin); P.D.P. Pharoah (Paul); B. Perkins (Barbara); M. Shah (Mitul); F. Blows (Fiona); D. Kang (Daehee); K.Y. Yoo; D-Y. Noh (Dong-Young); J.M. Hartman (Joost); X. Miao; K.S. Chia (Kee Seng); T.C. Putti (Thomas Choudary); U. Hamann (Ute); C. Luccarini (Craig); C. Baynes (Caroline); S. Ahmed (Shahana); M. Maranian (Melanie); S. Healey (Sue); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska-Bieniek (Katarzyna); K. Durda (Katarzyna); S. Sangrajrang (Suleeporn); V. Gaborieau (Valerie); P. Brennan (Paul); J.D. McKay (James); S. Slager (Susan); A.E. Toland (Amanda); D. Yannoukakos (Drakoulis); C-Y. Shen (Chen-Yang); C.-N. Hsiung (Chia-Ni); P.-E. Wu (Pei-Ei); S.-L. Ding (Shian-Ling); A. Ashworth (Alan); M. Jones (Michael); N. Orr (Nick); A.J. Swerdlow (Anthony ); H. Tsimiklis (Helen); E. Makalic (Enes); D.F. Schmidt (Daniel); Q.M. Bui (Quang); S.J. Chanock (Stephen); D. Hunter (David); R. Hein (Rebecca); N. Dahmen (N.); L. Beckmann (Lars); K. Aaltonen (Kirsimari); T.A. Muranen (Taru); T. Heikkinen (Tuomas); A. Irwanto (Astrid); N. Rahman (Nazneen); C. Turnbull (Clare); Q. Waisfisz (Quinten); E.J. Meijers-Heijboer (Hanne); M.A. Adank (Muriel); R. Van Der Luijt (Rob); P. Hall (Per); G. Chenevix-Trench (Georgia); A.M. Dunning (Alison); D.F. Easton (Douglas); A. Cox (Angela)

    2015-01-01

    textabstractPrevious studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucl

  12. Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk

    NARCIS (Netherlands)

    Wei-Yu Lin, Lin; Camp, Nicola J.; Ghoussaini, Maya; Beesley, Jonathan; Michailidou, Kyriaki; Hopper, John L.; Apicella, Carmel; Southey, Melissa C.; Stone, Jennifer; Schmidt, Marjanka K.; Broeks, Annegien; Van't Veer, Laura J.; Th Rutgers, Emiel J.; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Fasching, Peter A.; Haeberle, Lothar; Ekici, Arif B.; Beckmann, Matthias W.; Peto, Julian; Dos-Santos-Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Sawyer, Elinor J.; Cheng, Timothy; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Frederik Marmé, Marmé; Surowy, Harald M.; Burwinkel, Barbara; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Mulot, Claire; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Benitez, Javier; Pilar Zamora, M.; Perez, Jose Ignacio Arias; Menéndez, Primitiva; González-Neira, Anna; Pita, Guillermo; Rosario Alonso, M.; Álvarez, Nuria; Herrero, Daniel; Anton-Culver, Hoda; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Lichtner, Peter; Schmutzler, Rita K.; Müller-Myhsok, Bertram; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon Dschun; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Nevanlinna, Heli; Aittomäki, Kristiina; Blomqvist, Carl; Khan, Sofia; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Horio, Akiyo; Bogdanova, Natalia V.; Antonenkova, Natalia N.; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli Matti; Hartikainen, Jaana M.; Wu, Anna H.; Tseng, Chiu Chen; Van Den Berg, David; Stram, Daniel O.; Neven, Patrick; Wauters, Els; Wildiers, Hans; Lambrechts, Diether; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Bonanni, Bernardo; Couch, Fergus J.; Wang, Xianshu; Vachon, Celine; Purrington, Kristen; Giles, Graham G.; Milne, Roger L.; Mclean, Catriona; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Marchand, Loic Le; Simard, Jacques; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Teo, Soo Hwang; Yip, Cheng Har; Hassan, Norhashimah; Vithana, Eranga Nishanthie; Kristensen, Vessela; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha J.; Long, Jirong; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; Van Asperen, Christi J.; García-Closas, Montserrat; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Brand, Judith S.; Hooning, Maartje J.; Hollestelle, Antoinette; Van DenOuweland, Ans M W; Jager, Agnes; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Shu, Xiao Ou; Lu, Wei; Gao, Yu Tang; Cai, Hui; Cross, Simon S.; Reed, Malcolm W R; Blot, William; Signorello, Lisa B.; Cai, Qiuyin; Pharoah, Paul D P; Perkins, Barbara; Shah, Mitul; Blows, Fiona M.; Kang, Daehee; Yoo, Keun Young; Noh, Dong Young; Hartman, Mikael; Miao, Hui; Chia, Kee Seng; Putti, Thomas Choudary; Hamann, Ute; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Maranian, Mel; Healey, Catherine S.; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; Mckay, James; Slager, Susan; Toland, Amanda E.; Yannoukakos, Drakoulis; Shen, Chen Yang; Hsiung, Chia Ni; Wu, Pei Ei; Ding, Shian Ling; Ashworth, Alan; Jones, Michael; Orr, Nick; Swerdlow, Anthony J.; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel F.; Bui, Quang M.; Chanock, Stephen J.; Hunter, David J.; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Muranen, Taru A.; Heikkinen, Tuomas; Irwanto, Astrid; Rahman, Nazneen; Turnbull, Clare A.; Waisfisz, Quinten; Meijers-Heijboer, Hanne E J; Adank, Muriel A.; Van Der Luijt, Rob B.; Hall, Per; Chenevix-Trench, Georgia; Dunning, Alison; Easton, Douglas F.; Cox, Angela

    2015-01-01

    Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide polym

  13. Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk

    DEFF Research Database (Denmark)

    Lin, Wei-Yu; Camp, Nicola J; Ghoussaini, Maya

    2015-01-01

    Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide po...

  14. Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk

    NARCIS (Netherlands)

    Wei-Yu Lin, Lin; Camp, Nicola J.; Ghoussaini, Maya; Beesley, Jonathan; Michailidou, Kyriaki; Hopper, John L.; Apicella, Carmel; Southey, Melissa C.; Stone, Jennifer; Schmidt, Marjanka K.; Broeks, Annegien; Van't Veer, Laura J.; Th Rutgers, Emiel J.; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Fasching, Peter A.; Haeberle, Lothar; Ekici, Arif B.; Beckmann, Matthias W.; Peto, Julian; Dos-Santos-Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Sawyer, Elinor J.; Cheng, Timothy; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Frederik Marmé, Marmé; Surowy, Harald M.; Burwinkel, Barbara; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Mulot, Claire; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Benitez, Javier; Pilar Zamora, M.; Perez, Jose Ignacio Arias; Menéndez, Primitiva; González-Neira, Anna; Pita, Guillermo; Rosario Alonso, M.; Álvarez, Nuria; Herrero, Daniel; Anton-Culver, Hoda; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Lichtner, Peter; Schmutzler, Rita K.; Müller-Myhsok, Bertram; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon Dschun; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Nevanlinna, Heli; Aittomäki, Kristiina; Blomqvist, Carl; Khan, Sofia; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Horio, Akiyo; Bogdanova, Natalia V.; Antonenkova, Natalia N.; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli Matti; Hartikainen, Jaana M.; Wu, Anna H.; Tseng, Chiu Chen; Van Den Berg, David; Stram, Daniel O.; Neven, Patrick; Wauters, Els; Wildiers, Hans; Lambrechts, Diether; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Bonanni, Bernardo; Couch, Fergus J.; Wang, Xianshu; Vachon, Celine; Purrington, Kristen; Giles, Graham G.; Milne, Roger L.; Mclean, Catriona; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Marchand, Loic Le; Simard, Jacques; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Teo, Soo Hwang; Yip, Cheng Har; Hassan, Norhashimah; Vithana, Eranga Nishanthie; Kristensen, Vessela; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha J.; Long, Jirong; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; Van Asperen, Christi J.; García-Closas, Montserrat; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Brand, Judith S.; Hooning, Maartje J.; Hollestelle, Antoinette; Van DenOuweland, Ans M W; Jager, Agnes; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Shu, Xiao Ou; Lu, Wei; Gao, Yu Tang; Cai, Hui; Cross, Simon S.; Reed, Malcolm W R; Blot, William; Signorello, Lisa B.; Cai, Qiuyin; Pharoah, Paul D P; Perkins, Barbara; Shah, Mitul; Blows, Fiona M.; Kang, Daehee; Yoo, Keun Young; Noh, Dong Young; Hartman, Mikael; Miao, Hui; Chia, Kee Seng; Putti, Thomas Choudary; Hamann, Ute; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Maranian, Mel; Healey, Catherine S.; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; Mckay, James; Slager, Susan; Toland, Amanda E.; Yannoukakos, Drakoulis; Shen, Chen Yang; Hsiung, Chia Ni; Wu, Pei Ei; Ding, Shian Ling; Ashworth, Alan; Jones, Michael; Orr, Nick; Swerdlow, Anthony J.; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel F.; Bui, Quang M.; Chanock, Stephen J.; Hunter, David J.; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Muranen, Taru A.; Heikkinen, Tuomas; Irwanto, Astrid; Rahman, Nazneen; Turnbull, Clare A.; Waisfisz, Quinten; Meijers-Heijboer, Hanne E J; Adank, Muriel A.; Van Der Luijt, Rob B.; Hall, Per; Chenevix-Trench, Georgia; Dunning, Alison; Easton, Douglas F.; Cox, Angela

    2015-01-01

    Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide

  15. Improving global and regional resolution of male lineage differentiation by simple single-copy Y-chromosomal short tandem repeat polymorphisms

    NARCIS (Netherlands)

    M. Vermeulen (Mark); A. Wollstein (Andreas); K. van der Gaag (Kristiaan); O. Lao Grueso (Oscar); Y. Xue (Yali); Q. Wang (Qiuju); L. Roewer (Lutz); H. Knoblauch (Hans); C. Tyler-Smith (Chris); P. de Knijff (Peter); M.H. Kayser (Manfred)

    2009-01-01

    textabstractWe analyzed 67 short tandem repeat polymorphisms from the non-recombining part of the Y-chromosome (Y-STRs), including 49 rarely studied simple single-copy (ss)Y-STRs and 18 widely used Y-STRs, in 590 males from 51 populations belonging to 8 worldwide regions (HGDP-CEPH panel). Although

  16. RAG-dependent recombination at cryptic RSSs within TEL-AML1 t(12;21)(p13;q22) chromosomal translocation region.

    Science.gov (United States)

    Numata, Masashi; Saito, Shoko; Nagata, Kyosuke

    2010-11-26

    The recombination activating gene (RAG) is a lymphoid-specific endonuclease involved in the V(D)J recombination. It has long been proposed that mis-targeting of RAG proteins is one of the factors contributing to lymphoid chromosomal translocation bearing authentic recombination signal sequences (RSSs) in immunoglobulin (Ig) and T cell receptor (TCR) gene loci or cryptic RSSs (cRSSs). However, it is unclear whether primary sequence-dependent targeting mistake involved in the chromosomal translocation bearing no Ig/TCR gene loci is mediated by RAG proteins. Using an extrachromosomal recombination assay, we found RAG-dependent recombination in the regions dense in breakpoints within TEL and AML1 gene loci related to acute lymphoid leukemia-associated t(12;21)(p13;q22) chromosomal translocation. Sequence analyses revealed several heptamer-like sequences located in the vicinity of RAG-dependent recombination sites. By chromatin immunoprecipitation (ChIP) and ligation-mediated PCR (LM-PCR) assays, we have shown that RAG proteins bind to and cleave the TEL translocation region dense in breakpoints. These results suggest that mis-targeting of RAG proteins to cRSSs within TEL and AML1 translocation regions might be responsible for the t(12;21)(p13;q22) chromosomal translocation not bearing Ig/TCR regions. Copyright © 2010 Elsevier Inc. All rights reserved.

  17. Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk

    NARCIS (Netherlands)

    Wei-Yu Lin; N.J. Camp (Nicola); M. Ghoussaini (Maya); J. Beesley (Jonathan); K. Michailidou (Kyriaki); J. Hopper (John); C. Apicella (Carmel); M.C. Southey (Melissa); J. Stone (Jennifer); M.K. Schmidt (Marjanka); A. Broeks (Annegien); L.J. van 't Veer (Laura); E.J. Th Rutgers (Emiel J.); K.R. Muir (K.); A. Lophatananon (Artitaya); S. Stewart-Brown (Sarah); P. Siriwanarangsan (Pornthep); P.A. Fasching (Peter); L. Haeberle (Lothar); A.B. Ekici (Arif); M.W. Beckmann (Matthias W.); J. Peto (Julian); I. dos Santos Silva (Isabel); O. Fletcher (Olivia); N. Johnson (Nichola); M.K. Bolla (Manjeet); Q. Wang (Qing); J. Dennis (Joe); E.J. Sawyer (Elinor); T. Cheng (Timothy); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); Frederik Marmé; H. Surowy (Harald); B. Burwinkel (Barbara); P. Guénel (Pascal); T. Truong (Thérèse); F. Menegaux (Florence); C. Mulot (Claire); S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); S.F. Nielsen (Sune); H. Flyger (Henrik); J. Benítez (Javier); M.P. Zamora (Pilar); J.I.A. Perez (Jose Ignacio Arias); P. Menéndez (Primitiva); A. González-Neira (Anna); G. Pita (G.); M. Rosario Alonso; N. Álvarez (Nuria); D. Herrero (Daniel); H. Anton-Culver (Hoda); H. Brenner (Hermann); A.K. Dieffenbach (Aida Karina); V. Arndt (Volker); C. Stegmaier (Christa); A. Meindl (Alfons); P. Lichtner (Peter); R.K. Schmutzler (Rita); B. Müller-Myhsok (B.); H. Brauch (Hiltrud); T. Brüning (Thomas); Y.-D. Ko (Yon-Dschun)

    2014-01-01

    textabstractPrevious studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC).

  18. Bovine chromosomal regions affecting rheological traits in rennet-induced skim milk gels

    DEFF Research Database (Denmark)

    Gregersen, Vivi Raundahl; Gustavsson, F; Glantz, M

    2015-01-01

    Optimizing cheese yield and quality is of central importance to cheese manufacturing. The yield is associated with the time it takes before the gel has an optimal consistency for further processing, and it is well known that gel formation differs between individual milk samples. By identifying...... genomic regions affecting traits related to rennet-induced gelation, the aim of this study was to identify potential candidate genes affecting these traits. Hence, rennet-induced gelation, including rennet coagulation time, gel strength, and yield stress, was measured in skim milk samples collected from...

  19. Chromosome 5p Region SNPs Are Associated with Risk of NSCLC among Women

    Directory of Open Access Journals (Sweden)

    Alison L. Van Dyke

    2009-01-01

    Full Text Available In a population-based case-control study, we explored the associations between 42 polymorphisms in seven genes in this region and non-small cell lung cancer (NSCLC risk among Caucasian (364 cases; 380 controls and African American (95 cases; 103 controls women. Two TERT region SNPs, rs2075786 and rs2853677, conferred an increased risk of developing NSCLC, especially among African American women, and TERT-rs2735940 was associated with a decreased risk of lung cancer among African Americans. Five of the 20 GHR polymorphisms and SEPP1-rs6413428 were associated with a marginally increased risk of NSCLC among Caucasians. Random forest analysis reinforced the importance of GHR among Caucasians and identified AMACR, TERT, and GHR among African Americans, which were also significant using gene-based risk scores. Smoking-SNP interactions were explored, and haplotypes in TERT and GHR associated with NSCLC risk were identified. The roles of TERT, GHR, AMACR and SEPP1 genes in lung carcinogenesis warrant further exploration.

  20. Regional rearrangements in chromosome 15q21 cause formation of cryptic promoters for the CYP19 (aromatase) gene.

    Science.gov (United States)

    Demura, Masashi; Martin, Regina M; Shozu, Makio; Sebastian, Siby; Takayama, Kazuto; Hsu, Wei-Tong; Schultz, Roger A; Neely, Kirk; Bryant, Michael; Mendonca, Berenice B; Hanaki, Keiichi; Kanzaki, Susumu; Rhoads, David B; Misra, Madhusmita; Bulun, Serdar E

    2007-11-01

    Production of appropriate quantities of estrogen in various tissues is essential for human physiology. A single gene (CYP19), regulated via tissue-specific promoters, encodes the enzyme aromatase, which catalyzes the key step in estrogen biosynthesis. Aromatase excess syndrome is inherited as autosomal dominant and characterized by high systemic estrogen levels, short stature, prepubertal gynecomastia and testicular failure in males, and premature breast development and uterine pathology in females. The underlying genetic mechanism is poorly understood. Here, we characterize five distinct heterozygous rearrangements responsible for aromatase excess syndrome in three unrelated families and two individuals (nine patients). The constitutively active promoter of one of five ubiquitously expressed genes located within the 11.2 Mb region telomeric to the CYP19 gene in chromosome 15q21 cryptically upregulated aromatase expression in several tissues. Four distinct inversions reversed the transcriptional direction of the promoter of a gene (CGNL1, TMOD3, MAPK6 or TLN2), placing it upstream of the CYP19 coding region in the opposite strand, whereas a deletion moved the promoter of a fifth gene (DMXL2), normally transcribed from the same strand, closer to CYP19. The proximal breakpoints of inversions were located 17-185 kb upstream of the CYP19 coding region. Sequences at the breakpoints suggested that the inversions were caused by intrachromosomal nonhomologous recombination. Splicing the untranslated exon downstream of each promoter onto the identical junction upstream of the translation initiation site created CYP19 mRNA encoding functional aromatase protein. Taken together, small rearrangements may create cryptic promoters that direct inappropriate transcription of CYP19 or other critical genes.

  1. Placental hydroxymethylation vs methylation at the imprinting control region 2 on chromosome 11p15.5

    Directory of Open Access Journals (Sweden)

    H.R. Magalhaes

    2013-11-01

    Full Text Available In addition to methylated cytosines (5-mCs, hydroxymethylcytosines (5-hmCs are present in CpG dinucleotide-enriched regions and some transcription regulator binding sites. Unlike methylation, hydroxymethylation does not result in silencing of gene expression, and the most commonly used methods to study methylation, such as techniques based on restriction enzymatic digestion and/or bisulfite modification, are unable to distinguish between them. Genomic imprinting is a process of gene regulation where only one member of an allelic pair is expressed depending on the parental origin. Chromosome 11p15.5 has an imprinting control region (ICR2 that includes a differentially methylated region (KvDMR1 that guarantees parent-specific gene expression. The objective of the present study was to determine the presence of 5-hmC at the KvDMR1 in human placentas. We analyzed 16 third-trimester normal human placentas (chorionic villi. We compared two different methods based on real-time PCR after enzymatic digestion. The first method distinguished methylation from hydroxymethylation, while the other method did not. Unlike other methylation studies, subtle variations of methylation in ICRs could represent a drastic deregulation of the expression of imprinted genes, leading to important phenotypic consequences, and the presence of hydroxymethylation could interfere with the results of many studies. We observed agreement between the results of both methods, indicating the absence of hydroxymethylation at the KvDMR1 in third-trimester placentas. To the best of our knowledge, this is the first study describing the investigation of hydroxymethylation in human placenta using a genomic imprinting model.

  2. Placental hydroxymethylation vs methylation at the imprinting control region 2 on chromosome 11p15.5.

    Science.gov (United States)

    Magalhães, H R; Leite, S B P; Paz, C C P de; Duarte, G; Ramos, E S

    2013-10-22

    In addition to methylated cytosines (5-mCs), hydroxymethylcytosines (5-hmCs) are present in CpG dinucleotide-enriched regions and some transcription regulator binding sites. Unlike methylation, hydroxymethylation does not result in silencing of gene expression, and the most commonly used methods to study methylation, such as techniques based on restriction enzymatic digestion and/or bisulfite modification, are unable to distinguish between them. Genomic imprinting is a process of gene regulation where only one member of an allelic pair is expressed depending on the parental origin. Chromosome 11p15.5 has an imprinting control region (ICR2) that includes a differentially methylated region (KvDMR1) that guarantees parent-specific gene expression. The objective of the present study was to determine the presence of 5-hmC at the KvDMR1 in human placentas. We analyzed 16 third-trimester normal human placentas (chorionic villi). We compared two different methods based on real-time PCR after enzymatic digestion. The first method distinguished methylation from hydroxymethylation, while the other method did not. Unlike other methylation studies, subtle variations of methylation in ICRs could represent a drastic deregulation of the expression of imprinted genes, leading to important phenotypic consequences, and the presence of hydroxymethylation could interfere with the results of many studies. We observed agreement between the results of both methods, indicating the absence of hydroxymethylation at the KvDMR1 in third-trimester placentas. To the best of our knowledge, this is the first study describing the investigation of hydroxymethylation in human placenta using a genomic imprinting model.

  3. Epigenetic silencing of genes and microRNAs within the imprinted Dlk1-Dio3 region at human chromosome 14.32 in giant cell tumor of bone

    OpenAIRE

    Lehner, Burkhard; Kunz, Pierre; Saehr, Heiner; Fellenberg, Joerg

    2014-01-01

    Background Growing evidence exists that the neoplastic stromal cell population (GCTSC) within giant cell tumors (GCT) originates from mesenchymal stem cells (MSC). In a previous study we identified a microRNA signature that differentiates between these cell types. Five differentially expressed microRNAs are located within the Dlk1-Dio3 region on chromosome 14. Aberrant regulation within this region is known to influence cell growth, differentiation and the development of cancer. The aim of th...

  4. Haplotype frequencies in a sub-region of chromosome 19q13.3, related to risk and prognosis of cancer, differ dramatically between ethnic groups

    DEFF Research Database (Denmark)

    Schierup, M.H.; Mailund, T.; Li, H.

    2009-01-01

    Background: A small region of about 70 kb on human chromosome 19q13.3 encompasses 4 genes of which 3, ERCC1, ERCC2, and PPP1R13L (aka RAI) are related to DNA repair and cell survival, and one, CD3EAP, aka ASE1, may be related to cell proliferation. The whole region seems related to the cellular r...

  5. Haplotype frequencies in a sub-region of chromosome 19q13.3, related to risk and prognosis of cancer, differ dramatically between ethnic groups

    DEFF Research Database (Denmark)

    Schierup, M.H.; Mailund, T.; Li, H.

    2009-01-01

    Background: A small region of about 70 kb on human chromosome 19q13.3 encompasses 4 genes of which 3, ERCC1, ERCC2, and PPP1R13L (aka RAI) are related to DNA repair and cell survival, and one, CD3EAP, aka ASE1, may be related to cell proliferation. The whole region seems related to the cellular r...

  6. Molecular dissection of a contiguous gene syndrome: Frequent submicroscopic deletions, evolutionarily conserved sequences, and a hypomethylated island in the Miller-Dieker chromosome region

    Energy Technology Data Exchange (ETDEWEB)

    Ledbetter, D.H.; Ledbetter, S.A.; vanTuinen, P.; Summers, K.M.; Robinson, T.J.; Nakamura, Yusuke; Wolff, R.; White, R.; Barker, D.F.; Wallace, M.R.; Collins, F.S.; Dobyns, W.B. (Baylor College of Medicine, Houston, TX (USA))

    1989-07-01

    The Miller-Dieker syndrome (MDS), composed of characteristic facial abnormalities and a severe neuronal migration disorder affecting the cerebral cortex, is caused by visible or submicroscopic deletions of chromosome band 17p13. Twelve anonymous DNA markers were tested against a panel of somatic cell hybrids containing 17p deletions from seven MDS patients. All patients, including three with normal karyotypes, are deleted for a variable set of 5-12 markers. Two highly polymorphic VNTR (variable number of tandem repeats) probes, YNZ22 and YNH37, are codeleted in all patients tested and make molecular diagnosis for this disorder feasible. By pulsed-field gel electrophoresis, YNZ22 and YNH37 were shown to be within 30 kilobases (kb) of each other. Cosmid clones containing both VNTR sequences were identified, and restriction mapping showed them to be <15 kb apart. Three overlapping cosmids spanning >100 kb were completely deleted in all patients, providing a minimum estimate of the size of the MDS critical region. A hypomethylated island and evolutionarily conserved sequences were identified within this 100-kb region, indications of the presence of one or more expressed sequences potentially involved in the pathophysiology of this disorder. The conserved sequences were mapped to mouse chromosome 11 by using mouse-rat somatic cell hybrids, extending the remarkable homology between human chromosome 17 and mouse chromosome 11 by 30 centimorgans, into the 17p telomere region.

  7. Social responsiveness, an autism endophenotype: genomewide significant linkage to two regions on chromosome 8.

    Science.gov (United States)

    Lowe, Jennifer K; Werling, Donna M; Constantino, John N; Cantor, Rita M; Geschwind, Daniel H

    2015-03-01

    Autism spectrum disorder is characterized by deficits in social function and the presence of repetitive and restrictive behaviors. Following a previous test of principle, the authors adopted a quantitative approach to discovering genes contributing to the broader autism phenotype by using social responsiveness as an endophenotype for autism spectrum disorder. Linkage analyses using scores from the Social Responsiveness Scale were performed in 590 families from the Autism Genetic Resource Exchange, a largely multiplex autism spectrum disorder cohort. Regional and genomewide association analyses were performed to search for common variants contributing to social responsiveness. Social Responsiveness Scale scores were unimodally distributed in male offspring from multiplex autism families, in contrast with a bimodal distribution observed in female offspring. In correlated analyses differing by Social Responsiveness Scale respondent, genomewide significant linkage for social responsiveness was identified at chr8p21.3 (multipoint LOD=4.11; teacher/parent scores) and chr8q24.22 (multipoint LOD=4.54; parent-only scores), respectively. Genomewide or linkage-directed association analyses did not detect common variants contributing to social responsiveness. The sex-differential distributions of Social Responsiveness Scale scores in multiplex autism families likely reflect mechanisms contributing to the sex ratio for autism observed in the general population and form a quantitative signature of reduced penetrance of inherited liability to autism spectrum disorder among females. The identification of two strong loci for social responsiveness validates the endophenotype approach for the identification of genetic variants contributing to complex traits such as autism spectrum disorder. While causal mutations have yet to be identified, these findings are consistent with segregation of rare genetic variants influencing social responsiveness and underscore the increasingly

  8. Effect of the genetic background on recombination frequency in the cn-vg region of the second chromosome of natural populations of Drosophila melanogaster.

    Science.gov (United States)

    Hofmanová, J

    1975-01-01

    Newly established test stocks made it possible to follow the effect of three different defined genetic backgrounds (first and third chromosomes) on recombination frequency in the cn-vg region of the second chromosomes isolated from four natural populations of Drosophila melanogaster. One background was composed of the chromosomes with inversions obtained from the stock (see article) and another two backgrounds were of the standard type consisting one-half of the original chromosomes from the natural population and one-half of the chromosomes of the stocks Oregon R or Samarkand. Using the analysis of variance significant differences in RF values were found between and within populations and especially between the different backgrounds. Some simple and double interactions between the above factors played a role. The highest RF values were obtained on the background [corrected] with inversions. The effect of the different genetic backgrounds [corrected] by the action of the genetic modifiers of RF. The different genetic backgrounds affected the variations in RF values in individual populations and the different populations reacted differentially to the changed genetic background. The design of the experiment permitted an estimation of the causal compoenents of variance and heritability of RF from the sib analysis. The additive component of variance was present in only two of the populations under test; the respective estimates of heritability were very low.

  9. A genome-wide linkage study of bipolar disorder and co-morbid migraine: replication of migraine linkage on chromosome 4q24, and suggestion of an overlapping susceptibility region for both disorders on chromosome 20p11.

    Science.gov (United States)

    Oedegaard, K J; Greenwood, T A; Lunde, A; Fasmer, O B; Akiskal, H S; Kelsoe, J R

    2010-04-01

    Migraine and Bipolar Disorder (BPAD) are clinically heterogeneous disorders of the brain with a significant, but complex, genetic component. Epidemiological and clinical studies have demonstrated a high degree of co-morbidity between migraine and BPAD. Several genome-wide linkage studies in BPAD and migraine have shown overlapping regions of linkage on chromosomes, and two functionally similar voltage-dependent calcium channels CACNA1A and CACNA1C have been identified in familial hemiplegic migraine and recently implicated in two whole genome BPAD association studies, respectively. We hypothesized that using migraine co-morbidity to look at subsets of BPAD families in a genetic linkage analysis would prove useful in identifying genetic susceptibility regions in both of these disorders. We used BPAD with co-morbid migraine as an alternative phenotype definition in a re-analysis of the NIMH Bipolar Genetics Initiative wave 4 data set. In this analysis we selected only those families in which at least two members were diagnosed with migraine by a doctor according to patients' reports. Nonparametric linkage analysis performed on 31 families segregating both BPAD and migraine identified a linkage signal on chromosome 4q24 for migraine (but not BPAD) with a peak LOD of 2.26. This region has previously been implicated in two independent migraine linkage studies. In addition we identified a locus on chromosome 20p11 with overlapping elevated LOD scores for both migraine (LOD=1.95) and BPAD (LOD=1.67) phenotypes. This region has previously been implicated in two BPAD linkage studies, and, interestingly, it harbors a known potassium dependant sodium/calcium exchanger gene, SLC24A3, that plays a critical role in neuronal calcium homeostasis. Our findings replicate a previously identified migraine linkage locus on chromosome 4 (not co-segregating with BPAD) in a sample of BPAD families with co-morbid migraine, and suggest a susceptibility locus on chromosome 20, harboring a

  10. Physical mapping of a large plant genome using global high-information-content-fingerprinting: the distal region of the wheat ancestor Aegilops tauschii chromosome 3DS

    Directory of Open Access Journals (Sweden)

    You Frank M

    2010-06-01

    Full Text Available Abstract Background Physical maps employing libraries of bacterial artificial chromosome (BAC clones are essential for comparative genomics and sequencing of large and repetitive genomes such as those of the hexaploid bread wheat. The diploid ancestor of the D-genome of hexaploid wheat (Triticum aestivum, Aegilops tauschii, is used as a resource for wheat genomics. The barley diploid genome also provides a good model for the Triticeae and T. aestivum since it is only slightly larger than the ancestor wheat D genome. Gene co-linearity between the grasses can be exploited by extrapolating from rice and Brachypodium distachyon to Ae. tauschii or barley, and then to wheat. Results We report the use of Ae. tauschii for the construction of the physical map of a large distal region of chromosome arm 3DS. A physical map of 25.4 Mb was constructed by anchoring BAC clones of Ae. tauschii with 85 EST on the Ae. tauschii and barley genetic maps. The 24 contigs were aligned to the rice and B. distachyon genomic sequences and a high density SNP genetic map of barley. As expected, the mapped region is highly collinear to the orthologous chromosome 1 in rice, chromosome 2 in B. distachyon and chromosome 3H in barley. However, the chromosome scale of the comparative maps presented provides new insights into grass genome organization. The disruptions of the Ae. tauschii-rice and Ae. tauschii-Brachypodium syntenies were identical. We observed chromosomal rearrangements between Ae. tauschii and barley. The comparison of Ae. tauschii physical and genetic maps showed that the recombination rate across the region dropped from 2.19 cM/Mb in the distal region to 0.09 cM/Mb in the proximal region. The size of the gaps between contigs was evaluated by comparing the recombination rate along the map with the local recombination rates calculated on single contigs. Conclusions The physical map reported here is the first physical map using fingerprinting of a complete

  11. A polymorphic and hypervariable locus in the pseudoautosomal region of the CBA/H mouse sex chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Fennelly, J.; Laval, S.; Wright, E.; Plumb, M. [MRC Radiation and Genomic Stability Unit, Oxon (United Kingdom)

    1996-04-01

    We have identified a genomic locus (DXYH1) that is polymorphic and hypervariable within the CBA/H colony. Using a panel of C57BL/6 x Mus spretus backcross offspring, it was mapped to the distal end of the X chromosome. Pseudoautosomal inheritance was demonstrated through three generations of CBA/H x CBA/H and CBA/H x C57BL/6 crosses and confirmed through linkage to the Sxr locus in X/Y Sxr x 3H1 crosses. Meiotic recombination frequencies place DXYH1 {approximately}28% into the pseudoautosomal region from the boundary. The de novo generation of CBA/H variant DXYH1 restriction fragment length polymorphisms during spermatogenesis is suggestive of the germline instability associated with hypermutable human minisatellites. The absence of DXY1-related sequences in Mus spretus provides DNA sequence evidence to support the observed failure of X-Y pairing during meiosis and consequent hybrid infertility in C57BL/6 x Mus spretus male F1 offspring. 19 refs., 4 figs.

  12. Genes encoding two lipoproteins in the leuS-dacA region of the Escherichia coli chromosome

    Energy Technology Data Exchange (ETDEWEB)

    Takase, I.; Ishino, F.; Wachi, M.; Kamata, H.; Doi, M.; Asoh, S.; Matsuzawa, H.; Ohta, T.; Matsuhashi, M.

    1987-12-01

    The coding of two rare lipoproteins by two genes, rlpA and rlpB, located in the leuS-dacA region (15 min) on the Escherichia coli chromosome was demonstrated by expression of subcloned genes in a maxicell system. The formation of these two proteins was inhibited by globomycin, which is an inhibitor of the signal peptidase for the known lipoproteins of E. coli. In each case, this inhibition was accompanied by formation of a new protein, which showed a slightly lower mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and which we suppose to be a prolipoprotein with an N-terminal signal peptide sequence similar to those of the bacterial major lipoproteins and lysis proteins of some bacteriocins. The incorporation of /sup 3/H-labeled palmitate and glycerol into the two lipoproteins was also observed. Sequencing of DNA showed that the two lipoprotein genes contained sequences that could code for signal peptide sequences of 17 amino acids (rlpA lipoprotein) and 18 amino acids (rlpB lipoprotein). The deduced sequences of the mature peptides consisted of 345 amino acids (M/sub r/ 35,615, rlpA lipoprotein) and 175 amino acids (M/sub r/ 19,445, rlpB lipoprotein), with an N-terminal cysteine to which thioglyceride and N-fatty acyl residues may be attached. These two lioproteins may be important in duplication of the cells.

  13. Generation of an integrated transcription map of the BRCA2 region on chromosome 13q12-q13

    Energy Technology Data Exchange (ETDEWEB)

    Couch, F.J.; Peng, Yi; Thakur, Sanjay [Univ. of Pennsylvania, Philadelphia, PA (United States)] [and others

    1996-08-15

    An integrated approach involving physical mapping, identification of transcribed sequences, and computational analysis of genomic sequence was used to generate a detailed transcription map of the 1.0-Mb region containing the breast cancer susceptibility locus BRCA2 on chromosome 13q12-q13. This region is included in the genetic interval bounded by D13S1444 and D13S310. Retrieved sequences from exon amplification or hybrid selection procedures were grouped into physical intervals and subsequently grouped into transcription units by clone overlap. Overlap was established by direct hybridization, cDNA library screening, PCR cDNA linking (island hopping), and/or sequence alignment. Extensive genomic sequencing was performed in an effort to understand transcription unit organization. In total, approximately 500 kb of genomic sequence was completed. The transcription units were further characterized by hybridization to RNA from a series of human tissues. Evidence for seven genes, two putative pseudogenes, and nine additional putative transcription units was obtained. One of the transcription units was recently identified as BRCA2 but all others are novel genes of unknown function as only limited alignment to sequences in public databases was observed. Several retrieved transcribed sequences were not aligned into transcription units because no corresponding cDNAs were obtained when screening libraries or because of a lack of definitive evidence for splicing signals or putative coding sequence based on computational analysis. However, the presence of additional genes in the BRCA2 interval is suggested as groups of putative exons and hybrid selected clones that were transcribed in consistent orientations could be localized to common physical intervals. 25 refs., 2 figs., 3 tabs.

  14. Mapping of the human dentin matrix acidic phosphoprotein gene (DMP1) to the dentinogenesis imperfecta type II critical region at chromosome 4q21

    Energy Technology Data Exchange (ETDEWEB)

    Aplin, H.M.; Hirst, K.L.; Crosby, A.H.; Dixon, M.J. [Univ. of Manchester (United Kingdom)

    1995-11-20

    Dentinogenesis imperfecta type II (DGI1) is an autosomal dominant disorder of dentin formation, which has been mapped to human chromosome 4q12-q21. The region most likely to contain the DGI1 locus is a 3.2-cM region surrounding the osteopontin (SPP1) locus. Recently, a novel dentin-specific acidic phosphoprotein (dmp1) has been cloned in the rat and mapped to mouse chromosome 5q21. In the current investigation, we have isolated a cosmid containing the human DMP1 gene. The isolation of a short tandem repeat polymorphism at this locus has allowed us to map the DMP1 locus to human chromosome 4q21 and demonstrate that it is tightly linked to DGI1 in two families (Z{sub max} = 11.01, {theta} = 0.001). The creation of a yeast artificial chromosome contig around SPP1 has further allowed us to demonstrate that DMP1 is located within 150 kb of the bone sialoprotein and 490 kb of the SPP1 loci, respectively. DMP1 is therefore a strong candidate for the DGI1 locus. 12 refs., 2 figs., 1 tab.

  15. Mechanisms for chromosome segregation.

    Science.gov (United States)

    Bouet, Jean-Yves; Stouf, Mathieu; Lebailly, Elise; Cornet, François

    2014-12-01

    Bacteria face the problem of segregating their gigantic chromosomes without a segregation period restricted in time and space, as Eukaryotes do. Segregation thus involves multiple activities, general or specific of a chromosome region and differentially controlled. Recent advances show that these various mechanisms conform to a “pair and release” rule, which appears as a general rule in DNA segregation. We describe the latest advances in segregation of bacterial chromosomes with emphasis on the different pair and release mechanisms.

  16. The Paternal Landscape along the Bight of Benin – Testing Regional Representativeness of West-African Population Samples Using Y-Chromosomal Markers

    Science.gov (United States)

    Larmuseau, Maarten H. D.; Vessi, Andrea; Jobling, Mark A.; Van Geystelen, Anneleen; Primativo, Giuseppina; Biondi, Gianfranco; Martínez-Labarga, Cristina; Ottoni, Claudio; Decorte, Ronny; Rickards, Olga

    2015-01-01

    Patterns of genetic variation in human populations across the African continent are still not well studied in comparison with Eurasia and America, despite the high genetic and cultural diversity among African populations. In population and forensic genetic studies a single sample is often used to represent a complete African region. In such a scenario, inappropriate sampling strategies and/or the use of local, isolated populations may bias interpretations and pose questions of representativeness at a macrogeographic-scale. The non-recombining region of the Y-chromosome (NRY) has great potential to reveal the regional representation of a sample due to its powerful phylogeographic information content. An area poorly characterized for Y-chromosomal data is the West-African region along the Bight of Benin, despite its important history in the trans-Atlantic slave trade and its large number of ethnic groups, languages and lifestyles. In this study, Y-chromosomal haplotypes from four Beninese populations were determined and a global meta-analysis with available Y-SNP and Y-STR data from populations along the Bight of Benin and surrounding areas was performed. A thorough methodology was developed allowing comparison of population samples using Y-chromosomal lineage data based on different Y-SNP panels and phylogenies. Geographic proximity turned out to be the best predictor of genetic affinity between populations along the Bight of Benin. Nevertheless, based on Y-chromosomal data from the literature two population samples differed strongly from others from the same or neighbouring areas and are not regionally representative within large-scale studies. Furthermore, the analysis of the HapMap sample YRI of a Yoruban population from South-western Nigeria based on Y-SNPs and Y-STR data showed for the first time its regional representativeness, a result which is important for standard population and forensic genetic applications using the YRI sample. Therefore, the uniquely

  17. The Paternal Landscape along the Bight of Benin - Testing Regional Representativeness of West-African Population Samples Using Y-Chromosomal Markers.

    Directory of Open Access Journals (Sweden)

    Maarten H D Larmuseau

    Full Text Available Patterns of genetic variation in human populations across the African continent are still not well studied in comparison with Eurasia and America, despite the high genetic and cultural diversity among African populations. In population and forensic genetic studies a single sample is often used to represent a complete African region. In such a scenario, inappropriate sampling strategies and/or the use of local, isolated populations may bias interpretations and pose questions of representativeness at a macrogeographic-scale. The non-recombining region of the Y-chromosome (NRY has great potential to reveal the regional representation of a sample due to its powerful phylogeographic information content. An area poorly characterized for Y-chromosomal data is the West-African region along the Bight of Benin, despite its important history in the trans-Atlantic slave trade and its large number of ethnic groups, languages and lifestyles. In this study, Y-chromosomal haplotypes from four Beninese populations were determined and a global meta-analysis with available Y-SNP and Y-STR data from populations along the Bight of Benin and surrounding areas was performed. A thorough methodology was developed allowing comparison of population samples using Y-chromosomal lineage data based on different Y-SNP panels and phylogenies. Geographic proximity turned out to be the best predictor of genetic affinity between populations along the Bight of Benin. Nevertheless, based on Y-chromosomal data from the literature two population samples differed strongly from others from the same or neighbouring areas and are not regionally representative within large-scale studies. Furthermore, the analysis of the HapMap sample YRI of a Yoruban population from South-western Nigeria based on Y-SNPs and Y-STR data showed for the first time its regional representativeness, a result which is important for standard population and forensic genetic applications using the YRI sample

  18. Exclusion of Linkage to the CDL1 Gene Region on Chromosome 3q26.3 in Some Familial Cases of Cornelia de Lange Syndrome

    Science.gov (United States)

    Krantz, Ian D.; Tonkin, Emma; Smith, Melanie; Devoto, Marcella; Bottani, Armand; Simpson, Claire; Hofreiter, Mary; Abraham, Vinod; Jukofsky, Lori; Conti, Brian P.; Strachan, Tom; Jackson, Laird

    2016-01-01

    Cornelia de Lange Syndrome (CdLS) is a complex developmental disorder consisting of characteristic facial features, limb abnormalities, hirsutism, ophthalmologic involvement, gastroesophageal dysfunction, hearing loss, as well as growth and neuro-developmental retardation. Most cases of CdLS appear to be sporadic. Familial cases are rare and indicate autosomal dominant inheritance. Several individuals with CdLS have been reported with chromosomal abnormalities, suggesting candidate genomic regions within which the causative gene(s) may lie. A CdLS gene location (CDL1) has been assigned to 3q26.3 based on phenotypic overlap with the duplication 3q syndrome (critical region 3q26.2-q27) and the report of a CdLS individual with a balanced de novo t(3;17)(q26.3;q23.1). It has been postulated that a gene within the dup3q critical region results in the CdLS when deleted or mutated. We have performed a linkage analysis to the minimal critical region for the dup3q syndrome (that encompasses the translocation breakpoint) on chromosome 3q in 10 rare familial cases of CdLS. Nineteen markers spanning a region of approximately 40 Mb (37 cM) were used. Results of a multipoint linkage analysis demonstrated total lod-scores that were negative across the chromosome 3q26-q27 region. In 4/10 families, lod-scores were less than −2 in the 2 cM region encompassing the translocation, while in the remaining 6/10 families, lod-scores could not exclude linkage to this region. These studies indicate that in some multicase families, the disease gene does not map to the CDL1 region at 3q26.3. PMID:11391654

  19. A 2-Mb YAC contig and physical map covering the chromosome 8q12 breakpoint cluster region in pleomorphic adenomas of the salivary glands.

    Science.gov (United States)

    Kas, K; Röijer, E; Voz, M; Meyen, E; Stenman, G; Van de Ven, W J

    1997-08-01

    Pleomorphic adenomas are benign epithelial tumors originating from the major and minor salivary glands. Extensive cytogenetic studies have demonstrated that they frequently show chromosome abnormalities involving chromosome 8, with consistent breakpoints at 8q12. In previous studies, we have shown that these breakpoints are located in a 9-cM interval between MOS/D8S285 and D8S260. Here, we describe directional chromosome walking studies starting from D8S260 as well as D8S285. Using the CEPH and ICRF YAC libraries, these studies resulted in the construction of two nonoverlapping YAC contigs of about 2 and 5 Mb, respectively. Initial fluorescence in situ hybridization (FISH) analysis suggested that the majority of 8q12 breakpoints clustered within the 2-Mb contig, which was mapped to the centromeric part of chromosome band 8q12. This contig has at least double coverage and consists of 34 overlapping YAC clones. The localization of the YACs was confirmed by FISH analysis. On the basis of mapping data of landmarks with an average spacing of 65 kb as well as restriction enzyme analysis, a long-range physical map was established for the chromosome region spanned by the 2-Mb contig. The relative positions of various known genes and expressed sequence tags within this contig were also determined. Subsequent FISH analyses of pleomorphic adenomas using YACs as well as cosmids revealed that all but two of the 8q12 breakpoints in the primary tumors tested mapped within a 300-kb interval between the MOS proto-oncogene and STS EM156. The target gene affected by the chromosome aberrations mapping within this interval was recently shown to be the PLAG1 gene, which encodes a novel zinc finger protein.

  20. Isolation of a Genomic Region Affecting Most Components of Metabolic Syndrome in a Chromosome-16 Congenic Rat Model.

    Directory of Open Access Journals (Sweden)

    Lucie Šedová

    Full Text Available Metabolic syndrome is a highly prevalent human disease with substantial genomic and environmental components. Previous studies indicate the presence of significant genetic determinants of several features of metabolic syndrome on rat chromosome 16 (RNO16 and the syntenic regions of human genome. We derived the SHR.BN16 congenic strain by introgression of a limited RNO16 region from the Brown Norway congenic strain (BN-Lx into the genomic background of the spontaneously hypertensive rat (SHR strain. We compared the morphometric, metabolic, and hemodynamic profiles of adult male SHR and SHR.BN16 rats. We also compared in silico the DNA sequences for the differential segment in the BN-Lx and SHR parental strains. SHR.BN16 congenic rats had significantly lower weight, decreased concentrations of total triglycerides and cholesterol, and improved glucose tolerance compared with SHR rats. The concentrations of insulin, free fatty acids, and adiponectin were comparable between the two strains. SHR.BN16 rats had significantly lower systolic (18-28 mmHg difference and diastolic (10-15 mmHg difference blood pressure throughout the experiment (repeated-measures ANOVA, P < 0.001. The differential segment spans approximately 22 Mb of the telomeric part of the short arm of RNO16. The in silico analyses revealed over 1200 DNA variants between the BN-Lx and SHR genomes in the SHR.BN16 differential segment, 44 of which lead to missense mutations, and only eight of which (in Asb14, Il17rd, Itih1, Syt15, Ercc6, RGD1564958, Tmem161a, and Gatad2a genes are predicted to be damaging to the protein product. Furthermore, a number of genes within the RNO16 differential segment associated with metabolic syndrome components in human studies showed polymorphisms between SHR and BN-Lx (including Lpl, Nrg3, Pbx4, Cilp2, and Stab1. Our novel congenic rat model demonstrates that a limited genomic region on RNO16 in the SHR significantly affects many of the features of metabolic

  1. Characterization of divIVA and other genes located in the chromosomal region downstream of the dcw cluster in Streptococcus pneumoniae.

    Science.gov (United States)

    Fadda, Daniela; Pischedda, Carla; Caldara, Fabrizio; Whalen, Michael B; Anderluzzi, Daniela; Domenici, Enrico; Massidda, Orietta

    2003-10-01

    We analyzed the chromosome region of Streptococcus pneumoniae located downstream of the division and cell wall (dcw) cluster that contains the homolog of the Bacillus subtilis cell division gene divIVA and some genes of unknown function. Inactivation of divIVA in S. pneumoniae resulted in severe growth inhibition and defects in cell shape, nucleoid segregation, and cell division. Inactivation of the ylm genes resulted in some morphological and/or division abnormalities, depending on the inactivated gene. Transcriptional analysis revealed a relationship between these genes and the ftsA and ftsZ cell division genes, also indicating that the connection between the dcw cluster and the divIVA region is more extensive than just chromosomal position and gene organization.

  2. Genome-wide association study to identify chromosomal regions associated with antibody response to Mycobacterium avium subspecies paratuberculosis in milk of Dutch Holstein-Friesians.

    Science.gov (United States)

    van Hulzen, K J E; Schopen, G C B; van Arendonk, J A M; Nielen, M; Koets, A P; Schrooten, C; Heuven, H C M

    2012-05-01

    Heritability of susceptibility to Johne's disease in cattle has been shown to vary from 0.041 to 0.159. Although the presence of genetic variation involved in susceptibility to Johne's disease has been demonstrated, the understanding of genes contributing to the genetic variance is far from complete. The objective of this study was to contribute to further understanding of genetic variation involved in susceptibility to Johne's disease by identifying associated chromosomal regions using a genome-wide association approach. Log-transformed ELISA test results of 265,290 individual Holstein-Friesian cows from 3,927 herds from the Netherlands were analyzed to obtain sire estimated breeding values for Mycobacterium avium subspecies paratuberculosis (MAP)-specific antibody response in milk using a sire-maternal grandsire model with fixed effects for parity, year of birth, lactation stage, and herd; a covariate for milk yield on test day; and random effects for sire, maternal grandsire, and error. For 192 sires with estimated breeding values with a minimum reliability of 70%, single nucleotide polymorphism (SNP) typing was conducted by a multiple SNP analysis with a random polygenic effect fitting 37,869 SNP simultaneously. Five SNP associated with MAP-specific antibody response in milk were identified distributed over 4 chromosomal regions (chromosome 4, 15, 18, and 28). Thirteen putative SNP associated with MAP-specific antibody response in milk were identified distributed over 10 chromosomes (chromosome 4, 14, 16, 18, 19, 20, 21, 26, 27, and 29). This knowledge contributes to the current understanding of genetic variation involved in Johne's disease susceptibility and facilitates control of Johne's disease and improvement of health status by breeding.

  3. Identification of paralogous HERV-K LTRs on human chromosomes 3, 4, 7 and 11 in regions containing clusters of olfactory receptor genes.

    Science.gov (United States)

    Nadezhdin, E V; Lebedev, Y B; Glazkova, D V; Bornholdt, D; Arman, I P; Grzeschik, K H; Hunsmann, G; Sverdlov, E D

    2001-07-01

    A locus harboring a human endogenous retroviral LTR (long terminal repeat) was mapped on the short arm of human chromosome 7 (7p22), and its evolutionary history was investigated. Sequences of two human genome fragments that were homologous to the LTR-flanking sequences were found in human genome databases: (1) an LTR-containing DNA fragment from region 3p13 of the human genome, which includes clusters of olfactory receptor genes and pseudogenes; and (2) a fragment of region 21q22.1 lacking LTR sequences. PCR analysis demonstrated that LTRs with highly homologous flanking sequences could be found in the genomes of human, chimp, gorilla, and orangutan, but were absent from the genomes of gibbon and New World monkeys. A PCR assay with a primer set corresponding to the sequence from human Chr 3 allowed us to detect LTR-containing paralogous sequences on human chromosomes 3, 4, 7, and 11. The divergence times for the LTR-flanking sequences on chromosomes 3 and 7, and the paralogous sequence on chromosome 21, were evaluated and used to reconstruct the order of duplication events and retroviral insertions. (1) An initial duplication event that occurred 14-17 Mya and before LTR insertion - produced two loci, one corresponding to that located on Chr 21, while the second was the ancestor of the loci on chromosomes 3 and 7. (2) Insertion of the LTR (most probably as a provirus) into this ancestral locus took place 13 Mya. (3) Duplication of the LTR-containing ancestral locus occurred 11 Mya, forming the paralogous modern loci on Chr 3 and 7.

  4. Mapping of the mouse homolog of the human runt domain gene, AML2, to the distal region of mouse chromosome 4

    Energy Technology Data Exchange (ETDEWEB)

    Avraham, K.B.; Copeland, N.G.; Jenkins, N.A. [National Cancer Institute-Frederick Cancer Research and Development Center, MD (United States)] [and others

    1995-01-20

    AML2 is a runt domain belonging to a group of transcription factors that appear to play a role in Drosophila embryogenesis and mammalian oncogenic transformation. AML2 maps to human chromosome 1p36, a region involved in the t(1;3)(p36;q21) translocation found in association with myelodysplastic syndrome (MDS), myeloproliferative disease (MPD), and acute nonlymphocytic leukemia. 9 refs., 1 fig.

  5. Mapping of a chromosome 12 region associated with airway hyperresponsiveness in a recombinant congenic mouse strain and selection of potential candidate genes by expression and sequence variation analyses.

    Directory of Open Access Journals (Sweden)

    Cynthia Kanagaratham

    Full Text Available In a previous study we determined that BcA86 mice, a strain belonging to a panel of AcB/BcA recombinant congenic strains, have an airway responsiveness phenotype resembling mice from the airway hyperresponsive A/J strain. The majority of the BcA86 genome is however from the hyporesponsive C57BL/6J strain. The aim of this study was to identify candidate regions and genes associated with airway hyperresponsiveness (AHR by quantitative trait locus (QTL analysis using the BcA86 strain. Airway responsiveness of 205 F2 mice generated from backcrossing BcA86 strain to C57BL/6J strain was measured and used for QTL analysis to identify genomic regions in linkage with AHR. Consomic mice for the QTL containing chromosomes were phenotyped to study the contribution of each chromosome to lung responsiveness. Candidate genes within the QTL were selected based on expression differences in mRNA from whole lungs, and the presence of coding non-synonymous mutations that were predicted to have a functional effect by amino acid substitution prediction tools. One QTL for AHR was identified on Chromosome 12 with its 95% confidence interval ranging from 54.6 to 82.6 Mbp and a maximum LOD score of 5.11 (p = 3.68 × 10(-3. We confirmed that the genotype of mouse Chromosome 12 is an important determinant of lung responsiveness using a Chromosome 12 substitution strain. Mice with an A/J Chromosome 12 on a C57BL/6J background have an AHR phenotype similar to hyperresponsive strains A/J and BcA86. Within the QTL, genes with deleterious coding variants, such as Foxa1, and genes with expression differences, such as Mettl21d and Snapc1, were selected as possible candidates for the AHR phenotype. Overall, through QTL analysis of a recombinant congenic strain, microarray analysis and coding variant analysis we identified Chromosome 12 and three potential candidate genes to be in linkage with airway responsiveness.

  6. Role of the pseudoautosomal region in sex-chromosome pairing during male meiosis: Meiotic studies in a man with a deletion of distal Xp

    Energy Technology Data Exchange (ETDEWEB)

    Mohandas, T.K.; Passage, M.B.; Yen, P.H.; Speed, R.M.; Chandley, A.C.; Shapiro, L.J. (Univ. of California, San Francisco, CA (United States))

    1992-09-01

    Meiotic studies were undertaken in a 24-year-old male patient with short stature, chondrodysplasia punctata, ichthyosis, steroid sulfatase deficiency, and mild mental retardation with an inherited cytologically visible deletion of distal Xp. Molecular investigations showed that the pseudoautosomal region as well as the steroid sulfatase gene were deleted, but telomeric sequences were present at the pter on the deleted X chromosome. A complete failure of sex-chromosome pairing was observed in the primary spermatocytes of the patient. Telomeric approaches between the sex chromosomes were made at zygotene in some cells, but XY synaptonemal complex was formed. The sex chromosomes were present as univalents at metaphase I, and germ-cell development was arrested between metaphase I and metaphase II in the vast majority of cells, consistent with the azoospermia observed in the patient. The failure of XY pairing in this individual indicates that the pseudoautosomal sequences play an important role in initiating XY pairing and formation of synaptonemal complex at meiosis. 36 refs., 6 figs.

  7. Strain of Synechocystis PCC 6803 with Aberrant Assembly of Photosystem II Contains Tandem Duplication of a Large Chromosomal Region.

    Science.gov (United States)

    Tichý, Martin; Bečková, Martina; Kopečná, Jana; Noda, Judith; Sobotka, Roman; Komenda, Josef

    2016-01-01

    Cyanobacterium Synechocystis PCC 6803 represents a favored model organism for photosynthetic studies. Its easy transformability allowed construction of a vast number of Synechocystis mutants including many photosynthetically incompetent ones. However, it became clear that there is already a spectrum of Synechocystis "wild-type" substrains with apparently different phenotypes. Here, we analyzed organization of photosynthetic membrane complexes in a standard motile Pasteur collection strain termed PCC and two non-motile glucose-tolerant substrains (named here GT-P and GT-W) previously used as genetic backgrounds for construction of many photosynthetic site directed mutants. Although, both the GT-P and GT-W strains were derived from the same strain constructed and described by Williams in 1988, only GT-P was similar in pigmentation and in the compositions of Photosystem II (PSII) and Photosystem I (PSI) complexes to PCC. In contrast, GT-W contained much more carotenoids but significantly less chlorophyll (Chl), which was reflected by lower level of dimeric PSII and especially trimeric PSI. We found that GT-W was deficient in Chl biosynthesis and contained unusually high level of unassembled D1-D2 reaction center, CP47 and especially CP43. Another specific feature of GT-W was a several fold increase in the level of the Ycf39-Hlip complex previously postulated to participate in the recycling of Chl molecules. Genome re-sequencing revealed that the phenotype of GT-W is related to the tandem duplication of a large region of the chromosome that contains 100 genes including ones encoding D1, Psb28, and other PSII-related proteins as well as Mg-protoporphyrin methylester cyclase (Cycl). Interestingly, the duplication was completely eliminated after keeping GT-W cells on agar plates under photoautotrophic conditions for several months. The GT-W strain without a duplication showed no obvious defects in PSII assembly and resembled the GT-P substrain. Although, we do not exactly

  8. Marker chromosomes.

    Science.gov (United States)

    Rao, Kiran Prabhaker; Belogolovkin, Victoria

    2013-04-01

    Marker chromosomes are a morphologically heterogeneous group of structurally abnormal chromosomes that pose a significant challenge in prenatal diagnosis. Phenotypes associated with marker chromosomes are highly variable and range from normal to severely abnormal. Clinical outcomes are very difficult to predict when marker chromosomes are detected prenatally. In this review, we outline the classification, etiology, cytogenetic characterization, and clinical consequences of marker chromosomes, as well as practical approaches to prenatal diagnosis and genetic counseling.

  9. The 172 kb prkA-addAB region from 83° to 97° of the Bacillus subtilis chromosome contains several dysfunctional genes, the glyB marker, many genes encoding transporter proteins, and the ubiquitous hit gene

    NARCIS (Netherlands)

    Noback, Michiel A.; Holsappel, Siger; Kiewiet, Rense; Terpstra, Peter; Wambutt, Rolf; Wedler, Holger; Venema, Gerard; Bron, Sierd

    1998-01-01

    A 171812 bp nucleotide sequence between prkA and addAB (83° to 97°) on the genetic map of the Bacillus subtilis 168 chromosome was determined and analysed. An accurate physical/genetic map of this previously poorly described chromosomal region was constructed. One hundred and seventy open reading fr

  10. The 172 kb prkA-addAB region from 83 degrees to 97 degrees of the Bacillus subtilis chromosome contains several dysfunctional genes, the glyB marker, many genes encoding transporter proteins, and the ubiquitous hit gene

    NARCIS (Netherlands)

    Noback, MA; Holsappel, S; Kiewiet, R; Terpstra, P; Wambutt, R; Wedler, H; Venema, G; Bron, S

    1998-01-01

    A 171812 bp nucleotide sequence between prkA and addAB (83 degrees to 97 degrees) on the genetic map of the Bacillus subtilis 168 chromosome was determined and analysed. An accurate physical/genetic map of this previously poorly described chromosomal region was constructed. One hundred and seventy o

  11. Microsatellite and single nucleotide polymorphisms in the β-globin locus control region-hypersensitive Site 2: SPECIFICITY of Tunisian βs chromosomes.

    Science.gov (United States)

    Ben Mustapha, Maha; Moumni, Imen; Zorai, Amine; Douzi, Kaïs; Ghanem, Abderraouf; Abbes, Salem

    2012-01-01

    The diversity of sickle cell disease severity is attributed to several cis acting factors, among them the single nucleotide polymorphisms (SNPs) and (AT) rich region in the β-locus control region (β-LCR). This contains five DNase I hypersensitive sites (HS) located 6 to 22 kb upstream to the ϵ gene. The most important of these is the HS2 (5' β-LCR-HS2), characterized by the presence of three different SNPs and a microsatellite region known to be in association with β(S) chromosomes in various populations. The aim of this study was to present the molecular investigation of the 5' β-LCR-HS2 site in normal and sickle cell disease individuals in order to determine if there is any correlation or specificity between these molecular markers, the β(S) Tunisian chromosomes and phenotypical expression of sickle cell disease. One hundred and twenty-four chromosomes from Tunisian individuals (49 β(S) carriers and 13 normal individuals) were screened by polymerase chain reaction (PCR) and sequencing for the polymorphic short tandem microsatellite repeats (AT)(X)N(12)(AT)(Y) and the three SNPs (rs7119428, rs9736333 and rs60240093) of the 5' β-LCR-HS2. Twelve configurations of the microsatellite motif were found with an ancestral configuration elaborated by ClustalW software. Normal and mutated alleles were observed at the homozygous and heterozygous states for the three SNPs. Correlation between microsatellites and SNPs suggests that mutant SNP alleles were mainly associated, in the homozygous sickle cell disease phenotype, with the (AT)(8)N(12)GT(AT)(7) configuration, whereas, normal SNP alleles were associated with the (AT)(X)N(12)(AT)(11) configurations in normal β(A) chromosomes. The correlation of these various configurations with Hb F expression was also investigated. The principal component analysis (PCA) showed the correlation between the homozygous sickle cell disease phenotype, mutated SNP alleles and the Benin microsatellite configuration (AT)(8)N(12)GT

  12. Identification of region-specific yeast artificial chromosomes using pools of Alu element-mediated polymerase chain reaction probes labeled via linear amplification

    Energy Technology Data Exchange (ETDEWEB)

    Cole, C.G.; Bobrow, M.; Bentley, D.R.; Dunham, I. (United Medical and Dental Schools of Guy' s and St. Thomas Hospitals, London Bridge, London, England (United Kingdom)); Patel, K.; Shipley, J.; Sheer, D. (Imperial Cancer Research Fund, London (United Kingdom))

    1992-12-01

    The ability to identify large numbers of yeast artificial chromosomes (YACS) specific to any given genomic region rapidly and efficiently enhances both the construction of clone maps and the isolation of region-specific landmarks (e.g., polymorphic markers). The authors describe a method of preparing region-specific single-stranded hybridization probes from Alu element-mediated polymerase chain reaction (Alu-PCR) products of somatic cell hybrids for YAC library screening. Pools of up to 50 cloned Alu-PCR products from an irradiation-reduced hybrid containing 22q11.2-q13.1 were labeled to high specific activity by linear amplification using a single vector primer. The resulting single-stranded probes were extensively competed to remove repetitive sequences, while retaining the full complexity of the probe. Extensive coverage of the region by YACs using multiple probe pools was demonstrated as many YACs were detected more than once. In situ analysis using chosen YACs confirmed that the clones were specific for the region. Thus, this pooled probe approach constitutes a rapid method to identify large numbers of YACs relevant to a large chromosomal region. 29 refs., 4 figs.

  13. Identification of region-specific yeast artificial chromosomes using pools of Alu element-mediated polymerase chain reaction probes labeled via linear amplification.

    Science.gov (United States)

    Cole, C G; Patel, K; Shipley, J; Sheer, D; Bobrow, M; Bentley, D R; Dunham, I

    1992-12-01

    The ability to identify large numbers of yeast artificial chromosomes (YACs) specific to any given genomic region rapidly and efficiently enhances both the construction of clone maps and the isolation of region-specific landmarks (e.g., polymorphic markers). We describe a method of preparing region-specific single-stranded hybridization probes from Alu element-mediated polymerase chain reaction (Alu-PCR) products of somatic cell hybrids for YAC library screening. Pools of up to 50 cloned Alu-PCR products from an irradiation-reduced hybrid containing 22q11.2-q13.1 were labeled to high specific activity by linear amplification using a single vector primer. The resulting single-stranded probes were extensively competed to remove repetitive sequences, while retaining the full complexity of the probe. Extensive coverage of the region by YACs using multiple probe pools was demonstrated as many YACs were detected more than once. In situ analysis using chosen YACs confirmed that the clones were specific for the region. Thus, this pooled probe approach constitutes a rapid method to identify large numbers of YACs relevant to a large chromosomal region.

  14. Medium-range restriction maps of five chromosomes of Leishmania infantum and localization of size-variable regions

    Energy Technology Data Exchange (ETDEWEB)

    Ravel, C.; Wincker, P.; Blaineau, C. [Faculte de Medecine, Montpellier (France)] [and others

    1996-08-01

    This report describes the localization of the gene coding for human deoxyhypusine synthase (DHPS) to human chromosome 19p13.11-p13.12 using fluorescence in situ hybridization and somatic cell hybridization analysis. DHPS plays a vital role in the modification of hypusine. 10 refs., 1 fig.

  15. The polycystic kidney disease 1 gene encodes a 14 kb transcript and lies within a duplicated region on chromosome 16

    NARCIS (Netherlands)

    C.J. Ward (Christopher); B. Peral (Belén); J. Hughes (Jim); S. Thomas (Siep); V. Gamble (Vicki); A.B. MacCarthy (Angela); J. Sloane-Stanley (Jackie); P. Buckle (Peter); P. Kearney (Peter); D. Higgs (Douglas); C. Ratcliffe; P.C. Harris (Peter); J.H. Roelfsema (Jeroen); L. Spruit (Lia); J.J. Saris (Jasper); H.G. Dauwerse (Hans); D. Peters (Dorien); M.H. Breuning (Martijn); M.D. Nellist (Mark); P.T. Brook-Carter (Phillip); M.M. Maheshwar (Magitha); I. Cordeiro (Isabel); H. Santos (Heloisa); P. Cabral (Pedro); J. Sampson (Julian); L.A.J. Janssen (Bart); A.L.W. Hesseling-Janssen (Arjenne); A.M.W. van den Ouweland (Ans); H.J.F.M.M. Eussen (Bert); S. Verhoef; D. Lindhout (Dick); D.J.J. Halley (Dicky)

    1994-01-01

    textabstractAutosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder that frequently results in renal fallure due to progressive cyst development. The major locus, PKD1, maps to 16p13.3. We identified a chromosome translocation associated with ADPKD that disrupts a gene (PBP

  16. Characterization of a DNA sequence family in the Prader-Willi/Angelman syndrome chromosome region in 15q11-q13

    Energy Technology Data Exchange (ETDEWEB)

    Dittrich, B.; Knoblauch, H.; Buiting, K.; Horsthemke, B. (Universitaetsklinikum Essen (Germany))

    1993-04-01

    IR4-3R (D15S11) is an anonymous DNA sequence from human chromosome 15. Using YAC cloning and restriction enzyme analysis, the authors have found that IR4-3R detects five related DNA sequences, which are spread over 700 kb within the Prader-Willi/Angelman syndrome chromosome region in 15q11-q 13. The RsaI and StyI polymorphisms, which were described previously, are associated with the most proximal copy of IR4-3R and are in strong linkage disequilibrium. IR4-3R represents the third DNA sequence family that has been identified in 15q11-q13. 14 refs., 2 figs., 1 tab.

  17. 20-Mb duplication of chromosome 9p in a girl with minimal physical findings and normal IQ: narrowing of the 9p duplication critical region to 6 Mb.

    Science.gov (United States)

    Bonaglia, Maria Clara; Giorda, Roberto; Carrozzo, Romeo; Roncoroni, Maria Elena; Grasso, Rita; Borgatti, Renato; Zuffardi, Orsetta

    2002-10-01

    We studied the case of a girl with a partial 9p duplication, dup(9)(p22.1 --> p13.1). Molecular cytogenetics studies defined the chromosome 9 rearrangement as a direct duplication of 20 Mb from D9S1213 to D9S52. Microsatellite analysis demonstrated the presence of a double dosage of the paternal alleles and demonstrated that the duplication occurred between sister chromatids. The patient's phenotype was almost normal, with a few minor anomalies (dolichocephaly, crowded teeth, high arched palate) and normal IQ. The breakpoint's location in this patient and previously reported cases suggest that the critical region for the 9p duplication syndrome lies within a 6-Mb portion of chromosome 9p22 between markers D9S267 and D9S1213.

  18. A locus for the nystagmus-associated form of episodic ataxia maps to an 11-cM region on chromosome 19p

    Energy Technology Data Exchange (ETDEWEB)

    Kramer, P.L.; Gancher, S.T.; Nutt, J.G. [Oregon Health Oregon Health Sciences Univ., Portland, OR (United States)] [and others

    1995-07-01

    Episodic ataxia (EA) is a rare neurological disorder characterized by attacks of generalized ataxia and near-normal neurological function between attacks. Most inherited cases are the result of an autosomal dominant condition with unknown neuropathology. It is heterogeneous and includes at least two distinct forms. In EA-1, attacks last minutes and interictal myokymia may be present. In EA-2, attacks may last hours and interictal nystagmus may occur. We reported linkage in four EA-1 families to chromosome 12p13 and identified mutations in these families in a potassium channel gene, KCNA1. Recently, we reported linkage in two EA-2 families to a 30-cM region on chromosome 19p. This report is based on members of the same two families and one additional kindred. 18 refs., 1 fig., 1 tab.

  19. AID induces double-strand breaks at immunoglobulin switch regions and c-MYC causing chromosomal translocations in yeast THO mutants.

    Science.gov (United States)

    Ruiz, José F; Gómez-González, Belén; Aguilera, Andrés

    2011-02-01

    Transcription of the switch (S) regions of immunoglobulin genes in B cells generates stable R-loops that are targeted by Activation Induced Cytidine Deaminase (AID), triggering class switch recombination (CSR), as well as translocations with c-MYC responsible for Burkitt's lymphomas. In Saccharomyces cerevisiae, stable R-loops are formed co-transcriptionally in mutants of THO, a conserved nuclear complex involved in mRNP biogenesis. Such R-loops trigger genome instability and facilitate deamination by human AID. To understand the mechanisms that generate genome instability mediated by mRNP biogenesis impairment and by AID, we devised a yeast chromosomal system based on different segments of mammalian S regions and c-MYC for the analysis of chromosomal rearrangements in both wild-type and THO mutants. We demonstrate that AID acts in yeast at heterologous S and c-MYC transcribed sequences leading to double-strand breaks (DSBs) which in turn cause chromosomal translocations via Non-Homologous End Joining (NHEJ). AID-induced translocations were strongly enhanced in yeast THO null mutants, consistent with the idea that AID-mediated DSBs depend on R-loop formation. Our study not only provides new clues to understand the role of mRNP biogenesis in preventing genome rearrangements and the mechanism of AID-mediated genome instability, but also shows that, once uracil residues are produced by AID-mediated deamination, these are processed into DSBs and chromosomal rearrangements by the general and conserved DNA repair functions present from yeast to human cells.

  20. AID induces double-strand breaks at immunoglobulin switch regions and c-MYC causing chromosomal translocations in yeast THO mutants.

    Directory of Open Access Journals (Sweden)

    José F Ruiz

    2011-02-01

    Full Text Available Transcription of the switch (S regions of immunoglobulin genes in B cells generates stable R-loops that are targeted by Activation Induced Cytidine Deaminase (AID, triggering class switch recombination (CSR, as well as translocations with c-MYC responsible for Burkitt's lymphomas. In Saccharomyces cerevisiae, stable R-loops are formed co-transcriptionally in mutants of THO, a conserved nuclear complex involved in mRNP biogenesis. Such R-loops trigger genome instability and facilitate deamination by human AID. To understand the mechanisms that generate genome instability mediated by mRNP biogenesis impairment and by AID, we devised a yeast chromosomal system based on different segments of mammalian S regions and c-MYC for the analysis of chromosomal rearrangements in both wild-type and THO mutants. We demonstrate that AID acts in yeast at heterologous S and c-MYC transcribed sequences leading to double-strand breaks (DSBs which in turn cause chromosomal translocations via Non-Homologous End Joining (NHEJ. AID-induced translocations were strongly enhanced in yeast THO null mutants, consistent with the idea that AID-mediated DSBs depend on R-loop formation. Our study not only provides new clues to understand the role of mRNP biogenesis in preventing genome rearrangements and the mechanism of AID-mediated genome instability, but also shows that, once uracil residues are produced by AID-mediated deamination, these are processed into DSBs and chromosomal rearrangements by the general and conserved DNA repair functions present from yeast to human cells.

  1. Mapping strategies: Chromosome 16 workshop. Final technical report

    Energy Technology Data Exchange (ETDEWEB)

    1989-12-31

    The following topics from a workshop on chromosome 16 are briefly discussed: genetic map of chromosome 16; chromosome breakpoint map of chromosome 16; integrated physical/genetic map of chromosome 16; pulsed field map of the 16p13.2--p13.3 region (3 sheets); and a report of the HGM10 chromosome 16 committee.

  2. Evidence for positive selection of taurine genes within a QTL region on chromosome X associated with testicular size in Australian Brahman cattle.

    Science.gov (United States)

    Lyons, Russell E; Loan, Nguyen To; Dierens, Leanne; Fortes, Marina R S; Kelly, Matthew; McWilliam, Sean S; Li, Yutao; Bunch, Rowan J; Harrison, Blair E; Barendse, William; Lehnert, Sigrid A; Moore, Stephen S

    2014-01-10

    Previous genome-wide association studies have identified significant regions of the X chromosome associated with reproductive traits in two Bos indicus-influenced breeds: Brahman cattle and Tropical Composites. Two QTL regions on this chromosome were identified in both breeds as strongly associated with scrotal circumference measurements, a reproductive trait previously shown to be useful for selection of young bulls. Scrotal circumference is genetically correlated with early age at puberty in both male and female offspring. These QTL were located at positions 69-77 and 81-92 Mb respectively, large areas each to which a significant number of potential candidate genes were mapped. To further characterise these regions, a bioinformatic approach was undertaken to identify novel non-synonymous SNP within the QTL regions of interest in Brahman cattle. After SNP discovery, we used conventional molecular assay technologies to perform studies of two candidate genes in both breeds. Non-synonymous SNP mapped to Testis-expressed gene 11 (Tex11) were associated (P Brahman and Tropical Composite cattle with greatest reproductive potential. Association of non-synonymous SNP presented here are a first step to functional genetic studies. Bovine species may serve as a model for studying the role of Tex11 in male fertility, warranting further in-depth molecular characterisation.

  3. A structural locus for coagulation factor XIIIA (F13A) is located distal to the HLA region on chromosome 6p in man.

    Science.gov (United States)

    Olaisen, B; Gedde-Dahl, T; Teisberg, P; Thorsby, E; Siverts, A; Jonassen, R; Wilhelmy, M C

    1985-01-01

    Linkage between the locus for coagulation factor XIIIA (F13A) and HLA-region genes has been revealed during a linkage study between F13A and approximately 40 other polymorphic marker genes. In males, the maximum lod score between F13A and HLA-region genes (HLA-A, -C, -B, -DR; C4A, -B; Bf; and/or C2) is 7.60 at theta 1 = .18. To GLO, the maximum lod score is 2.37 at theta 1 = .19; to PGM3, .22 at theta 1 = .35. Female data indicate a clear sex difference in recombination frequency between F13A and HLA. The present findings, in combination with earlier knowledge of PGM3/GLO/HLA localization and gene distances, show that F13A is distal to HLA on the short arm of chromosome 6 in man. It is thus likely that by including FXIIIA typing in linkage studies, the whole male 6p is within mapping distance of highly polymorphic, classical marker genes. Earlier findings that the Hageman factor gene (F12) is located in the same chromosomal region may indicate the presence of a coagulation factor gene cluster in this region.

  4. High-resolution genotyping of chromosome 8 in colon adenocarcinomas reveals recurrent break point but no gene mutation in the 8p21 region.

    Science.gov (United States)

    Mourra, Najat; Zeitoun, Guy; Portier, Guillaume; Blanche, Hélène; Tubacher, Emmanuel; Gressin, Laetitia; Flejou, Jean-François; Tiret, Emmanuel; Thomas, Gilles; Olschwang, Sylviane

    2008-06-01

    The prognosis of patients with colorectal cancer is largely determined by the tumor stage. In this respect, colorectal cancer with lymph node metastases has the worst prognosis. Accordingly, there is considerable clinical interest in understanding the genetic mechanisms underlying metastasis formation. The short arm of chromosome 8 is often lost in colorectal cancer and has been associated with the advanced stages. A common region of deletion has been identified in 8p21, and we investigate here the localization of the putative tumor suppressor gene. A series of 683 sporadic microsatellite stability colorectal tumor samples has been genotyped on 12 microsatellite loci encompassing the common deleted region. Allelic losses were identified in 50% of the cases and 10 break points have been evidenced between D8S1734 and D8S1810, reducing the region of interest to D8S1771-D8S131. Among the 21 genes mapped in this interval, 14 candidate genes have been retained for the sequencing analysis of 48 tumors with 8p allelic loss. No mutation was found, suggesting more complex mechanisms of inactivation or side effects of chromosome arm 8q duplication, which might be up-regulating oncogenes not located within the deleted region.

  5. Multiple sex-associated regions and a putative sex chromosome in zebrafish revealed by RAD mapping and population genomics.

    Science.gov (United States)

    Anderson, Jennifer L; Rodríguez Marí, Adriana; Braasch, Ingo; Amores, Angel; Hohenlohe, Paul; Batzel, Peter; Postlethwait, John H

    2012-01-01

    Within vertebrates, major sex determining genes can differ among taxa and even within species. In zebrafish (Danio rerio), neither heteromorphic sex chromosomes nor single sex determination genes of large effect, like Sry in mammals, have yet been identified. Furthermore, environmental factors can influence zebrafish sex determination. Although progress has been made in understanding zebrafish gonad differentiation (e.g. the influence of germ cells on gonad fate), the primary genetic basis of zebrafish sex determination remains poorly understood. To identify genetic loci associated with sex, we analyzed F(2) offspring of reciprocal crosses between Oregon *AB and Nadia (NA) wild-type zebrafish stocks. Genome-wide linkage analysis, using more than 5,000 sequence-based polymorphic restriction site associated (RAD-tag) markers and population genomic analysis of more than 30,000 single nucleotide polymorphisms in our *ABxNA crosses revealed a sex-associated locus on the end of the long arm of chr-4 for both cross families, and an additional locus in the middle of chr-3 in one cross family. Additional sequencing showed that two SNPs in dmrt1 previously suggested to be functional candidates for sex determination in a cross of ABxIndia wild-type zebrafish, are not associated with sex in our AB fish. Our data show that sex determination in zebrafish is polygenic and that different genes may influence sex determination in different strains or that different genes become more important under different environmental conditions. The association of the end of chr-4 with sex is remarkable because, unique in the karyotype, this chromosome arm shares features with known sex chromosomes: it is highly heterochromatic, repetitive, late replicating, and has reduced recombination. Our results reveal that chr-4 has functional and structural properties expected of a sex chromosome.

  6. Multiple sex-associated regions and a putative sex chromosome in zebrafish revealed by RAD mapping and population genomics.

    Directory of Open Access Journals (Sweden)

    Jennifer L Anderson

    Full Text Available Within vertebrates, major sex determining genes can differ among taxa and even within species. In zebrafish (Danio rerio, neither heteromorphic sex chromosomes nor single sex determination genes of large effect, like Sry in mammals, have yet been identified. Furthermore, environmental factors can influence zebrafish sex determination. Although progress has been made in understanding zebrafish gonad differentiation (e.g. the influence of germ cells on gonad fate, the primary genetic basis of zebrafish sex determination remains poorly understood. To identify genetic loci associated with sex, we analyzed F(2 offspring of reciprocal crosses between Oregon *AB and Nadia (NA wild-type zebrafish stocks. Genome-wide linkage analysis, using more than 5,000 sequence-based polymorphic restriction site associated (RAD-tag markers and population genomic analysis of more than 30,000 single nucleotide polymorphisms in our *ABxNA crosses revealed a sex-associated locus on the end of the long arm of chr-4 for both cross families, and an additional locus in the middle of chr-3 in one cross family. Additional sequencing showed that two SNPs in dmrt1 previously suggested to be functional candidates for sex determination in a cross of ABxIndia wild-type zebrafish, are not associated with sex in our AB fish. Our data show that sex determination in zebrafish is polygenic and that different genes may influence sex determination in different strains or that different genes become more important under different environmental conditions. The association of the end of chr-4 with sex is remarkable because, unique in the karyotype, this chromosome arm shares features with known sex chromosomes: it is highly heterochromatic, repetitive, late replicating, and has reduced recombination. Our results reveal that chr-4 has functional and structural properties expected of a sex chromosome.

  7. Genetic mapping of a locus for multiple ephiphyseal dysplasia (EDM2) to a region of chromosome 1 containing a type IX collagen gene

    Energy Technology Data Exchange (ETDEWEB)

    Briggs, M.D.; Choi, HiChang; Warman, M.L.; Loughlin, J.A.; Wordsworth, P.; Sykes, B.C.; Irven, C.M.M.; Smith, M.; Wynne-Davies, R.; Lipson, M.H. [and others

    1994-10-01

    Multiple epiphyseal dysplasia (MED) is a dominantly inherited chondrodysplasia characterized by mild short stature and early-onset osteoarthrosis. Some forms of MED clinically resemble another chondrodysplasia phenotype, the mild form of pseudoachondroplasia (PSACH). On the basis of their clinical similarities as well as similar ultra-structural and biochemical features in cartilage from some patients, it has been proposed that MED and PSACH belong to a single bone-dysplasia family. Recently, both mild and severe PSACH as well as a form of MED have been linked to the same interval on chromosome 19, suggesting that they may be allelic disorders. Linkage studies with the chromosome 19 markers were carried out in a large family with MED and excluded the previously identified interval. Using this family, we have identified a MED locus on the short arm of chromosome 1, in a region containing the gene (COL9A2) that encodes the {alpha}2 chain of type IX collagen, a structural component of the cartilage extracellular matrix. 39 refs., 3 figs., 3 tabs.

  8. Chromosome aberrations in human lymphocytes from the plateau region of the Bragg curve for a carbon-ion beam

    Science.gov (United States)

    Manti, L.; Durante, M.; Grossi, G.; Pugliese, M.; Scampoli, P.; Gialanella, G.

    2007-06-01

    Radiotherapy with high-energy carbon ion beams can be more advantageous compared to photons because of better physical dose distribution and higher biological efficiency in tumour cell sterilization. Despite enhanced normal tissue sparing, damage incurred by normal cells at the beam entrance is unavoidable and may affect the progeny of surviving cells in the form of inheritable cytogenetic alterations. Furthermore, the quality of the beam along the Bragg curve is modified by nuclear fragmentation of projectile and target nuclei in the body. We present an experimental approach based on the use of a polymethylmethacrylate (PMMA) phantom that allows the simultaneous exposure to a particle beam of several biological samples positioned at various depths along the beam path. The device was used to measure the biological effectiveness of a 60 MeV/amu carbon-ion beam at inducing chromosomal aberrations in G0-human peripheral blood lymphocytes. Chromosome spreads were obtained from prematurely condensed cells and all structural aberration types were scored in Fluorescence in situ Hybridization (FISH)-painted chromosomes 1 and 2. Our results show a marked increase with depth in the aberration frequency prior to the Bragg peak, which is consistent with a linear energy transfer (LET)-dependent increase in biological effectiveness.

  9. Arabidopsis PTD is required for type I crossover formation and affects recombination frequency in two different chromosomal regions.

    Science.gov (United States)

    Lu, Pingli; Wijeratne, Asela J; Wang, Zhengjia; Copenhaver, Gregory P; Ma, Hong

    2014-03-20

    In eukaryotes, crossovers together with sister chromatid cohesion maintain physical association between homologous chromosomes, ensuring accurate chromosome segregation during meiosis I and resulting in exchange of genetic information between homologues. The Arabidopsis PTD (Parting Dancers) gene affects the level of meiotic crossover formation, but its functional relationships with other core meiotic genes, such as AtSPO11-1, AtRAD51, and AtMSH4, are unclear; whether PTD has other functions in meiosis is also unknown. To further analyze PTD function and to test for epistatic relationships, we compared the meiotic chromosome behaviors of Atspo11-1 ptd and Atrad51 ptd double mutants with the relevant single mutants. The results suggest that PTD functions downstream of AtSPO11-1 and AtRAD51 in the meiotic recombination pathway. Furthermore, we found that meiotic defects in rck ptd and Atmsh4 ptd double mutants showed similar meiotic phenotypes to those of the relevant single mutants, providing genetic evidences for roles of PTD and RCK in the type I crossovers pathway. Moreover, we employed a pollen tetrad-based fluorescence method and found that the meiotic crossover frequencies in two genetic intervals were significantly reduced from 6.63% and 22.26% in wild-type to 1.14% and 6.36%, respectively, in the ptd-2 mutant. These results revealed new aspects of PTD function in meiotic crossover formation.

  10. Engineered chromosome-based genetic mapping establishes a 3.7 Mb critical genomic region for Down syndrome-associated heart defects in mice.

    Science.gov (United States)

    Liu, Chunhong; Morishima, Masae; Jiang, Xiaoling; Yu, Tao; Meng, Kai; Ray, Debjit; Pao, Annie; Ye, Ping; Parmacek, Michael S; Yu, Y Eugene

    2014-06-01

    Trisomy 21 (Down syndrome, DS) is the most common human genetic anomaly associated with heart defects. Based on evolutionary conservation, DS-associated heart defects have been modeled in mice. By generating and analyzing mouse mutants carrying different genomic rearrangements in human chromosome 21 (Hsa21) syntenic regions, we found the triplication of the Tiam1-Kcnj6 region on mouse chromosome 16 (Mmu16) resulted in DS-related cardiovascular abnormalities. In this study, we developed two tandem duplications spanning the Tiam1-Kcnj6 genomic region on Mmu16 using recombinase-mediated genome engineering, Dp(16)3Yey and Dp(16)4Yey, spanning the 2.1 Mb Tiam1-Il10rb and 3.7 Mb Ifnar1-Kcnj6 regions, respectively. We found that Dp(16)4Yey/+, but not Dp(16)3Yey/+, led to heart defects, suggesting the triplication of the Ifnar1-Kcnj6 region is sufficient to cause DS-associated heart defects. Our transcriptional analysis of Dp(16)4Yey/+ embryos showed that the Hsa21 gene orthologs located within the duplicated interval were expressed at the elevated levels, reflecting the consequences of the gene dosage alterations. Therefore, we have identified a 3.7 Mb genomic region, the smallest critical genomic region, for DS-associated heart defects, and our results should set the stage for the final step to establish the identities of the causal gene(s), whose elevated expression(s) directly underlie this major DS phenotype.

  11. Comprehensive gene-based association study of a chromosome 20 linked region implicates novel risk loci for depressive symptoms in psychotic illness.

    Directory of Open Access Journals (Sweden)

    T Bernard Bigdeli

    Full Text Available BACKGROUND: Prior genomewide scans of schizophrenia support evidence of linkage to regions of chromosome 20. However, association analyses have yet to provide support for any etiologically relevant variants. METHODS: We analyzed 2988 LD-tagging single nucleotide polymorphisms (SNPs in 327 genes on chromosome 20, to test for association with schizophrenia in 270 Irish high-density families (ISHDSF, N = 270 families, 1408 subjects. These SNPs were genotyped using an Illumina iSelect genotyping array which employs the Infinium assay. Given a previous report of novel linkage with chromosome 20p using latent classes of psychotic illness in this sample, association analysis was also conducted for each of five factor-derived scores based on the Operational Criteria Checklist for Psychotic Illness (delusions, hallucinations, mania, depression, and negative symptoms. Tests of association were conducted using the PDTPHASE and QPDTPHASE packages of UNPHASED. Empirical estimates of gene-wise significance were obtained by adaptive permutation of a the smallest observed P-value and b the threshold-truncated product of P-values for each locus. RESULTS: While no single variant was significant after LD-corrected Bonferroni-correction, our gene-dropping analyses identified loci which exceeded empirical significance criteria for both gene-based tests. Namely, R3HDML and C20orf39 are significantly associated with depressive symptoms of schizophrenia (P(emp<2×10⁻⁵ based on the minimum P-value and truncated-product methods, respectively. CONCLUSIONS: Using a gene-based approach to family-based association, R3HDML and C20orf39 were found to be significantly associated with clinical dimensions of schizophrenia. These findings demonstrate the efficacy of gene-based analysis and support previous evidence that chromosome 20 may harbor schizophrenia susceptibility or modifier loci.

  12. A gene catalogue of the euchromatic male-specific region of the horse Y chromosome: comparison with human and other mammals.

    Directory of Open Access Journals (Sweden)

    Nandina Paria

    Full Text Available Studies of the Y chromosome in primates, rodents and carnivores provide compelling evidence that the male specific region of Y (MSY contains functional genes, many of which have specialized roles in spermatogenesis and male-fertility. Little similarity, however, has been found between the gene content and sequence of MSY in different species. This hinders the discovery of species-specific male fertility genes and limits our understanding about MSY evolution in mammals. Here, a detailed MSY gene catalogue was developed for the horse--an odd-toed ungulate. Using direct cDNA selection from horse testis, and sequence analysis of Y-specific BAC clones, 37 horse MSY genes/transcripts were identified. The genes were mapped to the MSY BAC contig map, characterized for copy number, analyzed for transcriptional profiles by RT-PCR, examined for the presence of ORFs, and compared to other mammalian orthologs. We demonstrate that the horse MSY harbors 20 X-degenerate genes with known orthologs in other eutherian species. The remaining 17 genes are acquired or novel and have so far been identified only in the horse or donkey Y chromosomes. Notably, 3 transcripts were found in the heterochromatic part of the Y. We show that despite substantial differences between the sequence, gene content and organization of horse and other mammalian Y chromosomes, the functions of MSY genes are predominantly related to testis and spermatogenesis. Altogether, 10 multicopy genes with testis-specific expression were identified in the horse MSY, and considered likely candidate genes for stallion fertility. The findings establish an important foundation for the study of Y-linked genetic factors governing fertility in stallions, and improve our knowledge about the evolutionary processes that have shaped Y chromosomes in different mammalian lineages.

  13. BAC array CGH in patients with Velocardiofacial syndrome-like features reveals genomic aberrations on chromosome region 1q21.1

    Directory of Open Access Journals (Sweden)

    Estivill Xavier

    2009-12-01

    Full Text Available Abstract Background Microdeletion of the chromosome 22q11.2 region is the most common genetic aberration among patients with velocardiofacial syndrome (VCFS but a subset of subjects do not show alterations of this chromosome region. Methods We analyzed 18 patients with VCFS-like features by comparative genomic hybridisation (aCGH array and performed a face-to-face slide hybridization with two different arrays: a whole genome and a chromosome 22-specific BAC array. Putative rearrangements were confirmed by FISH and MLPA assays. Results One patient carried a combination of rearrangements on 1q21.1, consisting in a microduplication of 212 kb and a close microdeletion of 1.15 Mb, previously reported in patients with variable phenotypes, including mental retardation, congenital heart defects (CHD and schizophrenia. While 326 control samples were negative for both 1q21.1 rearrangements, one of 73 patients carried the same 212-kb microduplication, reciprocal to TAR microdeletion syndrome. Also, we detected four copy number variants (CNVs inherited from one parent (a 744-kb duplication on 10q11.22; a 160 kb duplication and deletion on 22q11.21 in two cases; and a gain of 140 kb on 22q13.2, not present in control subjects, raising the potential role of these CNVs in the VCFS-like phenotype. Conclusions Our results confirmed aCGH as a successful strategy in order to characterize additional submicroscopic aberrations in patients with VCF-like features that fail to show alterations in 22q11.2 region. We report a 212-kb microduplication on 1q21.1, detected in two patients, which may contribute to CHD.

  14. A comparative transcriptional map of a region of 250 kb on the human and mouse X chromosome between the G6PD and the FLN1 genes.

    Science.gov (United States)

    Rivella, S; Tamanini, F; Bione, S; Mancini, M; Herman, G; Chatterjee, A; Maestrini, E; Toniolo, D

    1995-08-10

    The transcriptional organization of the region of the mouse X chromosome between the G6pd and the Fln1 genes was studied in detail, and it was compared with the syntenic region of the human chromosome. A cosmid contig of 250 kb was constructed by screening mouse cosmid libraries with probes for human genes and with whole cosmids. Overlapping cosmids were aligned by comparing EcoRI and rare-cutter restriction enzyme digestions. The gene order and the orientation of transcription were determined by hybridization with fragments from the 5' and 3' moieties of each cDNA. Our work demonstrates that all of the new genes identified in human are present in the mouse. The size of the region, 250 kb, is also very similar, as are gene order and gene organization: the transcriptional organization in "domains" described in human is found to be identical in the mouse. The major difference detected is the much lower content in rare-cutter restriction sites, which is related to the lower G+C and CpG content of mouse DNA. The very high conservation that we have described suggests that a potent selective pressure has contributed to such conservation of gene organization.

  15. A comparative transcriptional map of a region of 250 kb on the human and mouse X chromosome between the G6PD and the FLN1 genes

    Energy Technology Data Exchange (ETDEWEB)

    Rivella, S.; Tamanini, F.; Bione, S.; Mancini, M. [Istituto de Genetica Biochinica ed Evoluzionistica, Pavia (Italy)] [and others

    1995-08-10

    The transcriptional organization of the region of the mouse X chromosome between the G6pd and the Fln1 genes was studied in detail, and it was compared with the syntenic region of the human chromosome. A cosmid contig of 250 kb was constructed by screening mouse cosmid libraries with probes for human genes and with whole cosmids. Overlapping cosmids were aligned by comparing EcoRI and rare-cutter restriction enzyme digestions. The gene order and the orientation of transcription were determined by hybridization with fragments from the 5{prime} and 3{prime} moieties of each cDNA. Our work demonstrates that all of the new genes identified in human are present in the mouse. The size of the region, 250 kb, is also very similar, as are gene order and gene organizations: the transcriptional organization in {open_quotes}domains{close_quotes} described in human is found to be identical in the mouse. The major difference detected is the much lower content in rare-cutter restriction sites, which is related to the lower G+C and CpG content of mouse DNA. The very high conservation that we have described suggests that a potent selective pressure has contributed to such conservation of gene organization. 17 refs., 4 figs.

  16. A complete YAC contig of the Prader-Willi/Angelman chromosome region (15q11-q13) and refined localization of the SNRPN gene

    Energy Technology Data Exchange (ETDEWEB)

    Mutirangura, A.; Jayakumar, A.; Sutcliffe, J.S.; Nakao, M.; McKinney, M.J.; Beaudet, A.L.; Chinault, A.C.; Ledbetter, D.H. (Baylor College of Medicine, Houston, TX (United States)); Buiting, K.; Horsthemke, B. (Institut fur Humangenetik (Germany))

    1993-12-01

    Since a previous report of a partial YAC contig of the Prader-Willi/Angelman chromosome region (15q11-q13), a complete contig spanning approximately 3.5 Mb has been developed. YACs were isolated from two human genomic libraries by PCR and hybridization screening methods. Twenty-three sequence-tagged sites (STSs) were mapped within the contig, a density of [approximately]1 per 200 kb. Overlaps between YAC clones were identified by Alu-PCR dot-blot analysis and confirmed by STS mapping or hybridization with ends of YAC inserts. The gene encoding small nuclear ribonucleoprotein-associated peptide N (SNRPN), recently identified as a candidate gene for Prader-Willi syndrome, was localized within this contig between markers PW71 and TD3-21. Loci mapped within and immediately flanking the Prader-Willi/Angelman chromosome region contig are ordered as follows: cen-IR39-ML34-IR4-3R-TD189-1-PW71-SNRPN-TD3-21-LS6-1-GABRB3,D15S97-GABRA5-IR10-1-CMW1-tel. This YAC contig will be a useful resource for more detailed physical mapping of the region, for generation of new DNA markers, and for mapping or cloning candidate genes for the Prader-Willi and Angelman syndromes. 36 refs., 2 figs., 2 tabs.

  17. Autosomal dominant familial spastic paraplegia: Reduction of the FSPI candidate region on chromosome 14q to 7 cM and locus heterogeneity

    Energy Technology Data Exchange (ETDEWEB)

    Gispert, S.; Santos, N.; Auburger, G.; Damen, R.; Voit, T. [University Hospital, Duesseldorf (Germany); Schulz, J.; Klockgether, T. [University Hospital, Tuebingen (Germany); Orozco, G. [Hospital Lenin, Holguin (Cuba); Kreuz, F. [Technical Univ., Dresden (Netherlands); Weissenbach, J. [Unite de Genetique, Paris (France)

    1995-01-01

    Three large pedigrees of Germany descent with autosomal dominant {open_quotes}pure{close_quotes} familial spastic paraplegia (FSP) were characterized clinically and genetically. Haplotype and linkage analyses, with microsatellites covering the FSP region on chromosome 14q (locus FSP1), were performed. In pedigree W, we found a haplotype that cosegregates with the disease and observed three crossing-over events, reducing the FSP1 candidate region to 7 cM; in addition, the observation of apparent anticipation in this family suggests a trinucleotide repeat expansion as the mutation. In pedigree D and S, the gene locus could be excluded from the whole FSP1 region, confirming the locus heterogeneity of autosomal dominant FSP. 11 refs., 2 figs., 2 tabs.

  18. Origin and domestication of papaya Yh chromosome

    Science.gov (United States)

    Sex in papaya is controlled by a pair of nascent sex chromosomes. Females are XX, and two slightly different Y chromosomes distinguish males (XY) and hermaphrodites (XYh). The hermaphrodite-specific region of the Yh chromosome (HSY) and its X chromosome counterpart were sequenced and analyzed previo...

  19. Telomere dysfunction and chromosome instability

    Energy Technology Data Exchange (ETDEWEB)

    Murnane, John P., E-mail: jmurnane@radonc.ucsf.edu [Department of Radiation Oncology, University of California San Francisco, 2340 Sutter Street, San Francisco, CA 94143-1331 (United States)

    2012-02-01

    The ends of chromosomes are composed of a short repeat sequence and associated proteins that together form a cap, called a telomere, that keeps the ends from appearing as double-strand breaks (DSBs) and prevents chromosome fusion. The loss of telomeric repeat sequences or deficiencies in telomeric proteins can result in chromosome fusion and lead to chromosome instability. The similarity between chromosome rearrangements resulting from telomere loss and those found in cancer cells implicates telomere loss as an important mechanism for the chromosome instability contributing to human cancer. Telomere loss in cancer cells can occur through gradual shortening due to insufficient telomerase, the protein that maintains telomeres. However, cancer cells often have a high rate of spontaneous telomere loss despite the expression of telomerase, which has been proposed to result from a combination of oncogene-mediated replication stress and a deficiency in DSB repair in telomeric regions. Chromosome fusion in mammalian cells primarily involves nonhomologous end joining (NHEJ), which is the major form of DSB repair. Chromosome fusion initiates chromosome instability involving breakage-fusion-bridge (B/F/B) cycles, in which dicentric chromosomes form bridges and break as the cell attempts to divide, repeating the process in subsequent cell cycles. Fusion between sister chromatids results in large inverted repeats on the end of the chromosome, which amplify further following additional B/F/B cycles. B/F/B cycles continue until the chromosome acquires a new telomere, most often by translocation of the end of another chromosome. The instability is not confined to a chromosome that loses its telomere, because the instability is transferred to the chromosome donating a translocation. Moreover, the amplified regions are unstable and form extrachromosomal DNA that can reintegrate at new locations. Knowledge concerning the factors promoting telomere loss and its consequences is

  20. Characterisation of the Nevoid basal cell carcinoma (Gorlin`s) syndrome (NBCCS) gene region on chromosome 9q22-q31

    Energy Technology Data Exchange (ETDEWEB)

    Morris, D.J.; Digweed, M.; Sperling, K. [Freie Universitaet, Berlin (Germany)] [and other

    1994-09-01

    Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominantly inherited malignancy-associated disease of unknown etiology. The gene has been mapped to chromosome 9q22-q31 by us and other groups, using linkage analysis and loss of heterozygosity studies. Subsequent linkage and haplotype analyses from 133 meioses in NBCCS families has refined the position of the gene between D9S12 and D9S287. Since the gene for Fanconi`s Anaemia type C (FAAC) has been assigned to the same 9q region, we have performed linkage analysis between FACC and NBCCCS in NBCCS families. No recombination has been observed between NBCCS and FACC and maximum lod scores of 34.98 and 11.94 occur for both diseases at the markers D9S196/D9S197. Southern blot analysis using an FACC cDNA probe has revealed no detectable rearrangements in our NBCCS patients. We have established a YAC contig spanning the region from D9S12 to D9S176 and STS content mapping in 22 YACs has allowed the ordering of 12 loci in the region, including the xeroderma pigmentosum type A (XPAC) gene, as follows: D9S151/D9S12P1 - D9S12P2 - D9S197 - D9S196 - D9S280 - FACC - D9S287/XPAC - D9S180 - D9S6 - D9S176. Using the contig we have been able to eliminate the {alpha}1 type XV collagen gene and the markers D9S119 and D9S297 from the NBCCS candidate region. Twelve YACs have been used to screen a chromosome 9 cosmid library and more than 1000 cosmids from the region have been identified to be used for the construction of a cosmid contig. A selection of these cosmids will be used for the isolation of coding sequencing from the region.

  1. High-density SNP association study of the 17q21 chromosomal region linked to autism identifies CACNA1G as a novel candidate gene.

    Science.gov (United States)

    Strom, S P; Stone, J L; Ten Bosch, J R; Merriman, B; Cantor, R M; Geschwind, D H; Nelson, S F

    2010-10-01

    Chromosome 17q11-q21 is a region of the genome likely to harbor susceptibility to autism (MIM(209850)) based on earlier evidence of linkage to the disorder. This linkage is specific to multiplex pedigrees containing only male probands (MO) within the Autism Genetic Resource Exchange (AGRE). Earlier, Stone et al.(1) completed a high-density single nucleotide polymorphism association study of 13.7 Mb within this interval, but common variant association was not sufficient to account for the linkage signal. Here, we extend this single nucleotide polymorphism-based association study to complete the coverage of the two-LOD support interval around the chromosome 17q linkage peak by testing the majority of common alleles in 284 MO trios. Markers within an interval containing the gene, CACNA1G, were found to be associated with Autism Spectrum Disorder at a locally significant level (P=1.9 × 10(-5)). While establishing CACNA1G as a novel candidate gene for autism, these alleles do not contribute a sufficient genetic effect to explain the observed linkage, indicating that there is substantial genetic heterogeneity despite the clear linkage signal. The region thus likely harbors a combination of multiple common and rare alleles contributing to the genetic risk. These data, along with earlier studies of chromosomes 5 and 7q3, suggest few if any major common risk alleles account for Autism Spectrum Disorder risk under major linkage peaks in the AGRE sample. This provides important evidence for strategies to identify Autism Spectrum Disorder genes, suggesting that they should focus on identifying rare variants and common variants of small effect.

  2. Chromosome 7q Region Associated with Female Rheumatoid Arthritis in a British Population Fails to Replicate in a North American Case-Control Series

    Science.gov (United States)

    Korman, Benjamin D; Seldin, Michael F; Taylor, Kimberly E; Le, Julie M; Lee, Annette T; Plenge, Robert M; Amos, Christopher I; Criswell, Lindsey A; Gregersen, Peter K; Kastner, Daniel L; Remmers, Elaine F

    2009-01-01

    Objective The single nucleotide polymorphism (SNP) rs11761231 on chromosome 7q has been reported as a sexually dimorphic marker for rheumatoid arthritis susceptibility in a British population. We sought to replicate this finding and better characterize susceptibility alleles in the region in a North American population. Methods DNA from two North American collections of RA patients and controls (1605 cases and 2640 controls) was genotyped for rs11761231 and 16 additional chromosome 7q tag SNPs using Sequenom iPlex assays. Association tests were performed for each collection and also separately contrasting male cases versus male controls and female cases versus female controls. Principal components analysis (EIGENSTRAT) was used to determine association with RA before and after adjusting for population stratification in the subset of the samples (772 cases and 1213 controls) with whole genome SNP data. Results We failed to replicate association of the 7q region with rheumatoid arthritis. Initially, rs11761231 showed evidence for association with RA in the NARAC collection (p=0.0076) and rs11765576 showed association with RA in both the NARAC (p = 0.019) and RA replication (p = 0.0013) collections. These markers also exhibited sexual differentiation. However, in the whole genome subset, neither SNP showed significant association with RA after correction for population stratification. Conclusion While two SNPs on chromosome 7q appeared to be associated with RA in a North American cohort, the significance of this finding did not withstand correction for population substructure. Our results emphasize the need to carefully account for population structure to avoid false positive disease associations. PMID:19116934

  3. A ring chromosome X in a child with features of Kabuki Make-up syndrome

    Energy Technology Data Exchange (ETDEWEB)

    McGinniss, M.J.; Spring, N.; Brown, D.H. [Children`s Hospital, San Diego, CA (United States)] [and others

    1994-09-01

    The clinical features of this female patient (severe developmental delay, prominent finger pads, long palpebral fissures, short stature and history of hypotonia) suggested a diagnosis of Kabuki Make-up syndrome (KMS). Cytogenetic analyses showed this patient had a small ring X chromosome in 83% of cells and the parents were karyotypically normal. We hypothesized that deletion or rearrangement of X chromosome-derived sequences might be associated with the KMS-like phenotype observed in this patient. The breakpoints and parental origin of this small ring X were ascertained using a combination of genotyping with highly informative STRs and quantitative Southern blotting. PCR-based genotyping showed this female patient was heterozygous for X-linked loci SBMA (Xq11-q12) and DXS227 (Xq13.1). Hemizygosity was observed at several loci: DMD STR-49 (Xp21.2), DXS101 (Xq21.3), FMR-1 (Xq27.3) and DXYS64 (Xq28). Genotyping results at MIC2 (Xp22.3) and DXYS156 were not informative. These molecular genetic data indicate a large deletion of the distal long arm of the X chromosome and suggest a partial deletion of the distal short arm consistent with a small ring X chromosome with breakpoints near p21.2 and q13.1. This ring X chromosome is paternally-derived based on the observation that only the maternal alleles are inherited at three loci: (DMD STR-49, DXS101, and FMR-1). Studies to determine if the XIST gene at Xq13.3 is present and functioning on the ring chromosome are underway.

  4. Analysis of microsatellite markers and single nucleotide polymorphisms in candidate genes for susceptibility to bipolar affective disorder in the chromosome 12Q24.31 region.

    Science.gov (United States)

    Shink, Eric; Harvey, Mario; Tremblay, Monique; Gagné, Bernard; Belleau, Pascal; Raymond, Catherine; Labbé, Michel; Dubé, Marie-Pierre; Lafrenière, Ronald G; Barden, Nicholas

    2005-05-05

    Previous results from our genetic analyses using pedigrees from a French Canadian population suggested that the interval delimited by markers D12S86 and D12S378 on chromosome 12 was the most probable genomic region to contain a susceptibility gene for affective disorders. Here we present a more detailed genetic analysis of a 7.7 Mb genomic region located on 12q24.31. This region was saturated with 20 microsatellite markers to refine the candidate region and linkage analysis performed in 41 families from the Saguenay-Lac-St-Jean (SLSJ) region of Quebec. The results of two point parametric analysis using MFLINK supported the presence of a susceptibility locus on chromosome 12q24.31. Association studies with microsatellite markers using a case/control sample from the same population (n = 401) and analyzed with CLUMP revealed significant allelic associations between the bipolar phenotype and markers NBG6 (P = 0.008) and NBG12 (P < 10(-3)). According to these results, we investigated candidate genes in the NBG12 area. We analyzed 32 genes for the presence of polymorphisms in coding sequences and intron/exon junctions and genotyped 22 non-synonymous SNPs in the SLSJ case/control sample. Two uncommon polymorphisms (minor allele frequency < or = 0.03) found in KIAA1595 and FLJ22471 genes, gave P-values below 0.05 with the T1 statistic. Moreover, using haplotype analysis, a nearly significant haplotypic association was observed at the HM74 gene. These results do not give strong support for a role in the susceptibility to bipolar disorder of any of these genes analyzed. However, the significance of rare polymorphisms should be explored by further analyses. Copyright 2005 Wiley-Liss, Inc.

  5. Genomic analysis of a 1 Mb region near the telomere of Hessian fly chromosome X2 and avirulence gene vH13

    Directory of Open Access Journals (Sweden)

    Chen Ming-Shun

    2006-01-01

    Full Text Available Abstract Background To have an insight into the Mayetiola destructor (Hessian fly genome, we performed an in silico comparative genomic analysis utilizing genetic mapping, genomic sequence and EST sequence data along with data available from public databases. Results Chromosome walking and FISH were utilized to identify a contig of 50 BAC clones near the telomere of the short arm of Hessian fly chromosome X2 and near the avirulence gene vH13. These clones enabled us to correlate physical and genetic distance in this region of the Hessian fly genome. Sequence data from these BAC ends encompassing a 760 kb region, and a fully sequenced and assembled 42.6 kb BAC clone, was utilized to perform a comparative genomic study. In silico gene prediction combined with BLAST analyses was used to determine putative orthology to the sequenced dipteran genomes of the fruit fly, Drosophila melanogaster, and the malaria mosquito, Anopheles gambiae, and to infer evolutionary relationships. Conclusion This initial effort enables us to advance our understanding of the structure, composition and evolution of the genome of this important agricultural pest and is an invaluable tool for a whole genome sequencing effort.

  6. The database of chromosome imbalance regions and genes resided in lung cancer from Asian and Caucasian identified by array-comparative genomic hybridization

    Directory of Open Access Journals (Sweden)

    Lo Fang-Yi

    2012-06-01

    Full Text Available Abstract Background Cancer-related genes show racial differences. Therefore, identification and characterization of DNA copy number alteration regions in different racial groups helps to dissect the mechanism of tumorigenesis. Methods Array-comparative genomic hybridization (array-CGH was analyzed for DNA copy number profile in 40 Asian and 20 Caucasian lung cancer patients. Three methods including MetaCore analysis for disease and pathway correlations, concordance analysis between array-CGH database and the expression array database, and literature search for copy number variation genes were performed to select novel lung cancer candidate genes. Four candidate oncogenes were validated for DNA copy number and mRNA and protein expression by quantitative polymerase chain reaction (qPCR, chromogenic in situ hybridization (CISH, reverse transcriptase-qPCR (RT-qPCR, and immunohistochemistry (IHC in more patients. Results We identified 20 chromosomal imbalance regions harboring 459 genes for Caucasian and 17 regions containing 476 genes for Asian lung cancer patients. Seven common chromosomal imbalance regions harboring 117 genes, included gain on 3p13-14, 6p22.1, 9q21.13, 13q14.1, and 17p13.3; and loss on 3p22.2-22.3 and 13q13.3 were found both in Asian and Caucasian patients. Gene validation for four genes including ARHGAP19 (10q24.1 functioning in Rho activity control, FRAT2 (10q24.1 involved in Wnt signaling, PAFAH1B1 (17p13.3 functioning in motility control, and ZNF322A (6p22.1 involved in MAPK signaling was performed using qPCR and RT-qPCR. Mean gene dosage and mRNA expression level of the four candidate genes in tumor tissues were significantly higher than the corresponding normal tissues (PP=0.06. In addition, CISH analysis of patients indicated that copy number amplification indeed occurred for ARHGAP19 and ZNF322A genes in lung cancer patients. IHC analysis of paraffin blocks from Asian Caucasian patients demonstrated that the frequency of

  7. Brachygnathia, cardiomegaly and renal hypoplasia syndrome (BCRHS) in Merino sheep maps to a 1.1-megabase region on ovine chromosome OAR2.

    Science.gov (United States)

    Shariflou, M R; Wade, C M; Kijas, J; McCulloch, R; Windsor, P A; Tammen, I; Nicholas, F W

    2013-04-01

    A genome scan was conducted to map the autosomal recessive lethal disorder brachygnathia, cardiomegaly and renal hypoplasia syndrome (BCRHS) in Poll Merino sheep. The scan involved 10 affected and 27 unaffected animals from a single Poll Merino/Merino sheep flock, which were genotyped with the Illumina Ovine SNP50 BeadChip. Association and homozygosity mapping analyses located the disorder in a region comprising 20 consecutive SNPs spanning 1.1 Mb towards the distal end of chromosome OAR2. All affected animals and none of the unaffected animals were homozygous for the associated haplotype in this region. These results provide the basis for identifying the causative mutation(s) and should enable the development of a DNA test to identify carriers in the Poll Merino sheep population. Understanding the molecular control of BCRHS may provide insight into the fundamental genetic control and regulation of the affected organ systems.

  8. Genomic insights into hybridization in a localized region of sympatr y between pewee sister species (Contopus sordidulus × C. virens) and their chromosomal patterns of differentiation

    Institute of Scientific and Technical Information of China (English)

    Joseph D Manthey; and Mark B Robbins

    2016-01-01

    Background: The Great Plains of the United States includes a large number of hybrid and contact zones between bird species. The amount of gene lfow between sister species in these zones ranges from very rare hybridization events to widespread and prevalent introgression. Some of these avian systems have been studied extensively, while others have been indeterminate of whether hybridization exists in areas of sympatry. Using genomic-level approaches allows investigation of genomic patterns of hybridization and gene lfow between species—or lack thereof. Methods: We investigated a narrow zone of sympatry in Nebraska, USA between pewee species (Contopus sordidu-lus and C. virens), for which no hybridization has been conifrmed. We used thousands of single nucleotide polymor-phisms to identify potential hybridization and investigate genomic patterns of differentiation between these two species. Results: We found evidence of multiple hybrid individuals in the contact zone. Little genomic variation was ifxed between species, but a large proportion had differentiated allele frequencies between species. There was a positive relationship between genetic differentiation and chromosome size. Conclusions: We provided the ifrst conclusive evidence of hybridization between C. sordidulus and C. virens, in a region where secondary contact likely occurred due to human disturbance and habitat modiifcation. The genomic patterns of differentiation affrm that these species split in the relatively recent past. Finally, the relationship of chro-mosome size and genetic differentiation may have resulted from differential rates of chromosomal recombination in songbirds and genetic differentiation between species largely due to genetic drift (possibly in concert with selection).

  9. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33

    DEFF Research Database (Denmark)

    Wang, Zhaoming; Zhu, Bin; Zhang, Mingfeng

    2014-01-01

    Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may pl...

  10. Modeling Chromosomes

    Science.gov (United States)

    Robertson, Carol

    2016-01-01

    Learning about chromosomes is standard fare in biology classrooms today. However, students may find it difficult to understand the relationships among the "genome", "chromosomes", "genes", a "gene locus", and "alleles". In the simple activity described in this article, which follows the 5E approach…

  11. Cloning and characterization of a novel gene (C17orf25) from the deletion region on chromosome 17p13.3 in hepatocelular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Using a combination of hybridization of PAC to a cDNA library and RACE technique, we isolated a novel cDNA, designated as C17orf25 (Chromosome 17 open reading frame 25, previously named it HC71A), from the deletion region on chromosome 17p13.3. The cDNA encodes a protein of 313 amino acids with a calculated molecular mass of 34.8 kDa. C17orf25 is divided into 10 exons and 9 introns, spanning 23 kb of genomic DNA. Northern blot analysis showed that the mRNA expression of C17orf25 was decreased in hepatocellular carcinoma samples as compared to adjacent noncancerous liver tissues from the same patients. The transfection of C17orf25 into the hepatocellular carcinoma cell SMMC7721 and overexpression could inhibit the cell growth. The above results indicate that C17orf25 is a novel human gene, and the cloning and preliminary characterization of C17orf25 is a prerequisite for further functional analysis of this novel gene in human hepatocellular carcinoma.

  12. Genotoxic biomonitoring study of population residing in pesticide contaminated regions in Göksu Delta: micronucleus, chromosomal aberrations and sister chromatid exchanges.

    Science.gov (United States)

    Ergene, Serap; Celik, Ayla; Cavaş, Tolga; Kaya, Filiz

    2007-10-01

    Pesticides are widely used throughout the world in agriculture to protect crops and in public health to control diseases. Nevertheless, exposure to pesticides represents a potential risk to humans. This paper describes a study of possible genetic damage in the people living in regions contaminated with complex mixture of pesticides in Göksu Delta. In this study, used methods were chromosomal aberration (CA), sister chromatid exchange analysis (SCE) in the peripheral blood lymphocytes, and micronucleus (MN) assay in the buccal epithelial cells. In the present investigation, 32 affected subjects consist of 16 smoking and 16 non-smokings and an equal number of control subjects were assessed for genome damage. Micronucleus (MN), Broken egg (BE), Karyorrhexis (KR), Karyolysis (KL) and Binucleus (BN) frequencies were higher in affected subjects than in controls. Smoking had a statistically significant effect on the Micronucleus, Karyorrhexis and Binucleus frequencies for both the control and the exposed group. Also smoking and exposure affected the frequency of sister chromatid exchange and chromosomal aberrations compared with control groups.

  13. Chromosome protein framework from proteome analysis of isolated human metaphase chromosomes.

    Science.gov (United States)

    Fukui, Kiichi; Uchiyama, Susumu

    2007-01-01

    We have presented a structural model of the chromosome based on its constituent proteins. Development of a method of mass isolation for intact human metaphase chromosomes and proteome analysis by mass spectrometry of the isolated chromosomal proteins enabled us to develop a four-layer structural model of human metaphase chromosomes. The model consists of four layers, each with different chromosomal protein sets, i.e., chromosome coating proteins (CCPs), chromosome peripheral proteins (CPPs), chromosome structural proteins (CSPs), and chromosome fibrous proteins (CFPs). More than 200 identified proteins have been classified and assigned to the four layers with each layer occupying a distinct region of the chromosome. CCPs are localized at the most outer regions of the chromosomes and they attach to the regions tentatively and occasionally. CCPs include mostly mitochondrial and cytoplasmic proteins, e.g., 70 kDa heat shock protein 9B and Hsp60. CPPs are also localized at the peripheral regions of the chromosomes, but as the essential part of the chromosomes. CPPs include nucleolin, lamin A/C, fibrillarin, etc. CSPs are the primary chromosomal structure proteins, and include topoisomerase IIalpha, condensin subunits, histones, etc. CFPs have a fibrous nature, e.g., beta-actin, vimentin, myosin II, tublin, etc. A data set of these proteins, which we developed, contains essential chromosome proteins with classified information based on this four-layer model and presents useful leads for further studies on chromosomal structure and function.

  14. Linkage and association analyses identify a candidate region for apoB level on chromosome 4q32.3 in FCHL families.

    Science.gov (United States)

    Wijsman, Ellen M; Rothstein, Joseph H; Igo, Robert P; Brunzell, John D; Motulsky, Arno G; Jarvik, Gail P

    2010-06-01

    Familial combined hyperlipidemia (FCHL) is a complex trait leading to cardiovascular disease (CVD) risk. Elevated levels and size of apolipoprotein B (apoB) and low-density lipoprotein (LDL) are associated with FCHL, which is genetically heterogeneous and is likely caused by rare variants. We carried out a linkage-based genome scan of four large FCHL pedigrees for apoB level that is independent of LDL: apoB level that is adjusted for LDL level and size. Follow-up included SNP genotyping in the region with the strongest evidence of linkage. Several regions with the evidence of linkage in individual pedigrees support the rare variant model. Evidence of linkage was strongest on chromosome 4q, with multipoint analysis in one pedigree giving LOD = 3.1 with a parametric model, and a log Bayes Factor = 1.5 from a Bayesian oligogenic approach. Of the 293 SNPs spanning the implicated region on 4q, rs6829588 completely explained the evidence of linkage. This SNP accounted for 39% of the apoB phenotypic variance, with heterozygotes for this SNP having a trait value that was approximately 30% higher than that of the high-frequency homozygote, thus identifying and considerably refining a strong candidate region. These results illustrate the advantage of using large pedigrees in the search for rare variants: reduced genetic heterogeneity within single pedigrees coupled with the large number of individuals segregating otherwise-rare single variants leads to high power to implicate such variants.

  15. Genetic and physical mapping of the Treacher Collins syndrome locus with respect to loci in the chromosome 5q3 region

    Energy Technology Data Exchange (ETDEWEB)

    Jabs, E.W.; Li, Xiang; Coss, C.; Taylor, E. (Johns Hopkins School of Medicine, Baltimore, MD (United States)); Lovett, M. (Univ. of Texas Southwestern Medical Center, San Antonio, TX (United States)); Yamaoka, L.H.; Speer, M.C. (Duke Univ. Medical Center, Durham, NC (United States)); Cadle, R.; Hall, B. (Univ. of Kentucky, Lexington, KY (United States)); Brown, K. (Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY (United States)) (and others)

    1993-10-01

    Treacher Collins syndrome is an autosomal dominant, craniofacial developmental disorder, and its locus (TCOF1) has been mapped to chromosome 5q3. To refine the location of the gene within this region, linkage analysis was performed among the TCOF1 locus and 12 loci (IL9, FGFA, GRL, D5S207, D5S210, D5S376, CSF1R, SPARC, D5S119, D5S209, D5S527, FGFR4) in 13 Treacher Collins syndrome families. The highest maximum lod score was obtained between loci TCOF1 and D5S210 (Z = 10.52; [theta] = 0.02 [+-] 0.07). The best order, IL9-GRL-D5S207/D5S210-CSF1R-SPARC-D5S119, and genetic distances among these loci were determined in the 40 CEPH families by multipoint linkage analysis. YAC clones were used to establish the order of loci, centromere-5[prime]GRL3[prime]-D5S207-D5S210-D5S376-CSF1R-SPARC-D5S119-telomere. By combining known physical mapping data with ours, the order of chromosome 5q3 markers is centomere-IL9-FGFA-5[prime]GRL3[prime]-D5s207-D5S210-D5S376-CSF1R-SPARC-D5S119-D5S209-FGFR4-telomere. Based on this order, haplotype analysis suggests that the TCOF1 locus resides distal CSF1R and proximal to SPARC within a region less than 1 Mb in size. 29 refs., 2 figs., 2 tabs.

  16. Microphthalmia with linear skin defects syndrome.

    Science.gov (United States)

    García-Rabasco, Ana; De-Unamuno, Blanca; Martínez, Francisco; Febrer-Bosch, Isabel; Alegre-de-Miquel, Víctor

    2013-01-01

    Microphthalmia with linear skin defects (MLS) or microcornea, dermal aplasia and sclerocornea (MIDAS) syndrome is a rare X-linked-dominant disorder. We present a patient with agenesis of corpus callosum, ocular abnormalities, and multiple skin defects. The cytogenetic studies of the MLS critical region (Xp22.2) were normal, but a skewed X-chromosome inactivation pattern (85:15) was observed.

  17. The Chromosome 9p21 CVD- and T2D-Associated Regions in a Norwegian Population (The HUNT2 Survey

    Directory of Open Access Journals (Sweden)

    Øyvind Helgeland

    2015-01-01

    Full Text Available Background. Two adjacent regions upstream CDKN2B on chromosome 9p21 have been associated with type 2 diabetes (T2D and progression of cardiovascular disease (CVD. The precise location and number of risk variants have not been completely delineated and a possible synergistic relationship between the adjacent regions is not fully addressed. By a population based cross-sectional case-control design, we genotyped 18 SNPs upstream of CDKN2B tagging 138 kb in and around two LD-blocks associated with CVD and T2D and investigated associations with T2D, angina pectoris (AP, myocardial infarction (MI, coronary heart disease (CHD; AP or AMI, and stroke using 5,564 subjects from HUNT2. Results. Single point and haplotype analysis showed evidence for only one common T2D risk haplotype (rs10757282∣rs10811661: OR = 1.19, P=2.0×10-3 in the region. We confirmed the strong association between SNPs in the 60 kb CVD region with AP, MI, and CHD (P<0.01. Conditioning on the lead SNPs in the region, we observed two suggestive independent single SNP association signals for MI, rs2065501  (P=0.03 and rs3217986  (P=0.04. Conclusions. We confirmed the association of known variants within the 9p21 interval with T2D and CHD. Our results further suggest that additional CHD susceptibility variants exist in this region.

  18. Fine mapping and association studies of a high-density lipoprotein cholesterol linkage region on chromosome 16 in French-Canadian subjects.

    Science.gov (United States)

    Dastani, Zari; Pajukanta, Päivi; Marcil, Michel; Rudzicz, Nicholas; Ruel, Isabelle; Bailey, Swneke D; Lee, Jenny C; Lemire, Mathieu; Faith, Janet; Platko, Jill; Rioux, John; Hudson, Thomas J; Gaudet, Daniel; Engert, James C; Genest, Jacques

    2010-03-01

    Low levels of high-density lipoprotein cholesterol (HDL-C) are an independent risk factor for cardiovascular disease. To identify novel genetic variants that contribute to HDL-C, we performed genome-wide scans and quantitative association studies in two study samples: a Quebec-wide study consisting of 11 multigenerational families and a study of 61 families from the Saguenay-Lac St-Jean (SLSJ) region of Quebec. The heritability of HDL-C in these study samples was 0.73 and 0.49, respectively. Variance components linkage methods identified a LOD score of 2.61 at 98 cM near the marker D16S515 in Quebec-wide families and an LOD score of 2.96 at 86 cM near the marker D16S2624 in SLSJ families. In the Quebec-wide sample, four families showed segregation over a 25.5-cM (18 Mb) region, which was further reduced to 6.6 Mb with additional markers. The coding regions of all genes within this region were sequenced. A missense variant in CHST6 segregated in four families and, with additional families, we observed a P value of 0.015 for this variant. However, an association study of this single-nucleotide polymorphism (SNP) in unrelated Quebec-wide samples was not significant. We also identified an SNP (rs11646677) in the same region, which was significantly associated with a low HDL-C (P=0.016) in the SLSJ study sample. In addition, RT-PCR results from cultured cells showed a significant difference in the expression of CHST6 and KIAA1576, another gene in the region. Our data constitute additional evidence for a locus on chromosome 16q23-24 that affects HDL-C levels in two independent French-Canadian studies.

  19. Sequence variations in the 5' flanking and IVS-II regions of the G gamma- and A gamma-globin genes of beta S chromosomes with five different haplotypes.

    Science.gov (United States)

    Lanclos, K D; Oner, C; Dimovski, A J; Gu, Y C; Huisman, T H

    1991-06-01

    We have amplified and sequenced the 5' flanking and the second intervening sequence (IVS-II) regions of both the G gamma- and A gamma-globin genes of the beta S chromosomes from sickle cell anemia (SS) patients with homozygosities for five different haplotypes. The sequencing data, compared with previously published sequences for the normal chromosomes A and B, show many similarities to chromosome B for haplotypes 19, 20, and 17, while haplotypes 3 and 31 are remarkably similar to chromosome A and also similar to each other. Several unique mutations were found in the 5' flanking regions (G gamma and A gamma) of haplotypes 19 and 20 and in the IVS-II segments of the same genes of haplotypes 19, 20, and 17; the IVS-II of haplotypes 3 and 31 were identical to those of chromosome A. Dot-blot analyses of amplified DNA from additional SS patients with specific probes have confirmed that these mutations are unique for each haplotype. The two general patterns that have been observed among the five haplotypes have most probably arisen by gene conversion events between the A and B type chromosomes in the African population. These patterns correlate with high and low fetal hemoglobin expression, and it is speculated that these and other yet unknown gene conversions may contribute to the variations in hemoglobin F and G gamma levels observed among SS patients. In vitro expression experiments involving the approximately 1.3-kb 5' flanking regions of the G gamma- and A gamma-globin genes of the beta S chromosomes with the five different haplotypes failed to detect differences between the levels of expression, suggesting that the sequence variations observed between these segments of DNA are not the primary cause of the differences in hemoglobin F levels among the SS patients.

  20. [Sex chromosomes and meiosis].

    Science.gov (United States)

    Guichaoua, M-R; Geoffroy-Siraudin, C; Tassistro, V; Ghalamoun-Slaimi, R; Perrin, J; Metzler-Guillemain, C

    2009-01-01

    Sex chromosome behaviour fundamentally differs between male and female meiosis. In oocyte, X chromosomes synapse giving a XX bivalent which is not recognizable in their morphology and behaviour from autosomal bivalents. In human male, X and Y chromosomes differ from one another in their morphology and their genetic content, leading to a limited pairing and preventing genetic recombination, excepted in homologous region PAR1. During pachytene stage of the first meiotic prophase, X and Y chromosomes undergo a progressive condensation and form a transcriptionally silenced peripheral XY body. The condensation of the XY bivalent during pachytene stage led us to describe four pachytene substages and to localize the pachytene checkpoint between substages 2 and 3. We also defined the pachytene index (PI=P1+P2/P1+P2+P3+P4) which is always less than 0.50 in normal meiosis. XY body undergoes decondensation at diplotene stage, but transcriptional inactivation of the two sex chromosomes or Meiotic Sex Chromosome Inactivation (MSCI) persists through to the end of spermatogenesis. Sex chromosome inactivation involves several proteins, some of them were now identified. Two isoforms of the HP1 protein, HP1beta and HP1gamma, are involved in the facultative heterochromatinization of the XY body, but the initiation of this process involves the phosphorylation of the protein H2AX by the kinase ATR whose recruitment depends on BRCA1. Extensive researches on the inactivation of the sex chromosomes during male meiosis will allow to a better understanding of some male infertilities.

  1. Genetic and physical fine mapping of the novel brown midrib gene bm6 in maize (Zea mays L.) to a 180 kb region on chromosome 2.

    Science.gov (United States)

    Chen, Yongsheng; Liu, Hongjun; Ali, Farhad; Scott, M Paul; Ji, Qing; Frei, Ursula Karoline; Lübberstedt, Thomas

    2012-10-01

    Brown midrib mutants in maize are known to be associated with reduced lignin content and increased cell wall digestibility, which leads to better forage quality and higher efficiency of cellulosic biomass conversion into ethanol. Four well known brown midrib (bm) mutants, named bm1-4, were identified several decades ago. Additional recessive brown midrib mutants have been identified by allelism tests and designated as bm5 and bm6. In this study, we determined that bm6 increases cell wall digestibility and decreases plant height. bm6 was confirmed onto the short arm of chromosome 2 by a small mapping set with 181 plants from a F(2) segregating population, derived from crossing B73 and a bm6 mutant line. Subsequently, 960 brown midrib individuals were selected from the same but larger F(2) population for genetic and physical mapping. With newly developed markers in the target region, the bm6 gene was assigned to a 180 kb interval flanked by markers SSR_308337 and SSR_488638. In this region, ten gene models are predicted in the maize B73 sequence. Analysis of these ten genes as well as genes in the syntenic rice region revealed that four of them are promising candidate genes for bm6. Our study will facilitate isolation of the underlying gene of bm6 and advance our understanding of brown midrib gene functions.

  2. Evaluation of chromosome 5 aberrations in complex karyotypes of patients with myeloid disorders reveals their contribution to dicentric and tricentric chromosomes, resulting in the loss of critical 5q regions.

    Science.gov (United States)

    Herry, Angèle; Douet-Guilbert, Nathalie; Morel, Frédéric; Le Bris, Marie-Josée; Morice, Patrick; Abgrall, Jean François; Berthou, Christian; De Braekeleer, Marc

    2007-06-01

    Dicentric chromosomes have often been observed in complex karyotypes in previously reported studies of therapy-related myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Fluorescence in situ hybridization (FISH) has now made the characterization of these rearrangements much easier. Dicentric and tricentric chromosomes were identified in 21 patients (9 MDS and 12 AML) among the 133 consecutive MDS/AML patients (17%) who had a structural or numerical aberration of chromosome 5 using conventional cytogenetic analysis. One third (7/21) of the patients had received alkylating drugs for a previously diagnosed cancer or chronic myeloproliferative disease. Loss of 5q material was identified in all 21 patients. One copy of the EGR1 (5q31) or the CSF1R (5q33 approximately q34) genes was lost in 20 of the 21 patients. Dicentric and tricentric chromosomes involving chromosome 5 are frequently observed in complex karyotypes among patients with de novo or therapy-related MDS/AML. They lead to deletions of various parts of the long arm of chromosome 5.

  3. Characterization of an Autism-Associated Segmental Maternal Heterodisomy of the Chromosome 15q11-13 Region

    Science.gov (United States)

    Kwasnicka-Crawford, Dorota A.; Roberts, Wendy; Scherer, Stephen W.

    2007-01-01

    Cytogenetic abnormalities in the Prader-Willi/Angelman syndrome (PWS/AS) critical region have been described in individuals with autism. Maternal duplications and linkage disequilibrium in families with autism suggest the existence of a susceptibility locus at 15q11-q13. Here, we describe a 6-year-old girl diagnosed with autism, developmental…

  4. Identification of genetic and environmental factors stimulating excision from Streptomyces scabiei chromosome of the toxicogenic region responsible for pathogenicity.

    Science.gov (United States)

    Chapleau, Mélanie; Guertin, Julien F; Farrokhi, Ali; Lerat, Sylvain; Burrus, Vincent; Beaulieu, Carole

    2016-05-01

    The genes conferring pathogenicity in Streptomyces turgidiscabies, a pathogen causing common scab of potato, are grouped together on a pathogenicity island (PAI), which has been found to be mobile and appears to transfer and disseminate like an integrative and conjugative element (ICE). However, in Streptomyces scabiei, another common scab-inducing species, the pathogenicity genes are clustered in two regions: the toxicogenic region (TR) and the colonization region. The S. scabiei 87.22 genome was analysed to investigate the potential mobility of the TR. Attachment sites (att), short homologous sequences that delineate ICEs, were identified at both extremities of the TR. An internal att site was also found, suggesting that the TR has a composite structure (TR1 and TR2). Thaxtomin biosynthetic genes, essential for pathogenicity, were found in TR1, whereas candidate genes with known functions in recombination, replication and conjugal transfer were found in TR2. Excision of the TR1 or TR2 subregions alone, or of the entire TR region, was observed, although the excision frequency of TR was low. However, the excision frequency was considerably increased in the presence of either mitomycin C or Streptomyces coelicolor cells. A composite TR structure was not observed in all S. scabiei and Streptomyces acidiscabies strains tested. Of the ten strains analysed, seven lacked TR2 and no TR excision event could be detected in these strains, thus suggesting the implication of TR2 in the mobilization of S. scabiei TR.

  5. Induction of chromosome aberrations is non-linear within the low dose region and depends on dose rate

    Energy Technology Data Exchange (ETDEWEB)

    Oudalova, A.A.; Geras' kin, S.A.; Dikarev, V.G.; Nesterov, Y.B.; Dikareva, N.S

    2002-07-01

    The low dose region was evaluated for meristem cells of spring barley. A study of the cytogenetic damage in the low dose range was carried out to determine the genuine shape of the dose curve. The relationship between the frequency of aberrant cells and the absorbed dose is shown to be non-linear with a site at low doses within which the cytogenetic damage exceeds the control level significantly and does not depend on dose value. Within the tested exposure region, the aberrant cell frequency is found to decrease with increasing dose rate, but the shape of the dose curve remained invariable. The piecewise linear model fits the experimental data much better than the linear one. (author)

  6. Genome instability in AZFc region on Y chromosome in leukocytes of fertile and infertile individuals following exposure to gamma radiation.

    Science.gov (United States)

    Moghbeli-Nejad, Sahar; Mozdarani, Hossein; Behmanesh, Mehrdad; Rezaiean, Zahra; Fallahi, Parvin

    2012-01-01

    Men are exposed to various doses of ionizing radiation due to living in regions with high natural background radiation, accidentally, occupationally or for cancer treatment. To study genomic instability of AZFc region to gamma radiation, blood samples from normal, oligozoospermia, and azoospermia individuals were irradiated by a Co-60 source. Irradiated cells were kept for 48 h in order to repair initial DNA damages. Real time PCR was performed for three markers (SY 1206, SY 1197, SY 579) for testing copy number variation before and after irradiation. Copy number variations were compared by calculation of cycle threshold comparative method. Copy number variations of studied markers in AZFc region (microdeletion and duplication) in all samples after exposure to radiation increased with a dose dependent fashion. The frequency of instability was significantly higher in samples from infertile men in comparison with fertile ones (p  0.05). This observation might be a possible explanation for induction of azoospermia and oligozoospermia after radiotherapy. Increased frequency of induced microdeletion and duplication in infertile men compared with normal might be attributed to the deficiency in repair systems and the genetic factors involved in incomplete spermatogenesis of infertile men.

  7. Verification of the Chromosome Region 9q21 Association with Pelvic Organ Prolapse Using RegulomeDB Annotations

    Directory of Open Access Journals (Sweden)

    Maryam B. Khadzhieva

    2015-01-01

    Full Text Available Pelvic organ prolapse (POP is a common highly disabling disorder with a large hereditary component. It is characterized by a loss of pelvic floor support that leads to the herniation of the uterus in or outside the vagina. Genome-wide linkage studies have shown an evidence of POP association with the region 9q21 and six other loci in European pedigrees. The aim of our study was to test the above associations in a case-control study in Russian population. Twelve SNPs including SNPs cited in the above studies and those selected using the RegulomeDB annotations for the region 9q21 were genotyped in 210 patients with POP (stages III-IV and 292 controls with no even minimal POP. Genotyping was performed using the polymerase chain reaction with confronting two-pair primers (PCR–CTPP. Association analyses were conducted for individual SNPs, 9q21 haplotypes, and SNP-SNP interactions. SNP rs12237222 with the highest RegulomeDB score 1a appeared to be the key SNP in haplotypes associated with POP. Other RegulomeDB Category 1 SNPs, rs12551710 and rs2236479 (scores 1d and 1f, resp., exhibited epistatic effects. In this study, we verified the region 9q21 association with POP in Russians, using RegulomeDB annotations.

  8. Investigating the prehistory of Tungusic peoples of Siberia and the Amur-Ussuri region with complete mtDNA genome sequences and Y-chromosomal markers.

    Directory of Open Access Journals (Sweden)

    Ana T Duggan

    Full Text Available Evenks and Evens, Tungusic-speaking reindeer herders and hunter-gatherers, are spread over a wide area of northern Asia, whereas their linguistic relatives the Udegey, sedentary fishermen and hunter-gatherers, are settled to the south of the lower Amur River. The prehistory and relationships of these Tungusic peoples are as yet poorly investigated, especially with respect to their interactions with neighbouring populations. In this study, we analyse over 500 complete mtDNA genome sequences from nine different Evenk and even subgroups as well as their geographic neighbours from Siberia and their linguistic relatives the Udegey from the Amur-Ussuri region in order to investigate the prehistory of the Tungusic populations. These data are supplemented with analyses of Y-chromosomal haplogroups and STR haplotypes in the Evenks, Evens, and neighbouring Siberian populations. We demonstrate that whereas the North Tungusic Evenks and Evens show evidence of shared ancestry both in the maternal and in the paternal line, this signal has been attenuated by genetic drift and differential gene flow with neighbouring populations, with isolation by distance further shaping the maternal genepool of the Evens. The Udegey, in contrast, appear quite divergent from their linguistic relatives in the maternal line, with a mtDNA haplogroup composition characteristic of populations of the Amur-Ussuri region. Nevertheless, they show affinities with the Evenks, indicating that they might be the result of admixture between local Amur-Ussuri populations and Tungusic populations from the north.

  9. Haplotype frequencies in a sub-region of chromosome 19q13.3, related to risk and prognosis of cancer, differ dramatically between ethnic groups

    Directory of Open Access Journals (Sweden)

    Wang Jun

    2009-03-01

    Full Text Available Abstract Background A small region of about 70 kb on human chromosome 19q13.3 encompasses 4 genes of which 3, ERCC1, ERCC2, and PPP1R13L (aka RAI are related to DNA repair and cell survival, and one, CD3EAP, aka ASE1, may be related to cell proliferation. The whole region seems related to the cellular response to external damaging agents and markers in it are associated with risk of several cancers. Methods We downloaded the genotypes of all markers typed in the 19q13.3 region in the HapMap populations of European, Asian and African descent and inferred haplotypes. We combined the European HapMap individuals with a Danish breast cancer case-control data set and inferred the association between HapMap haplotypes and disease risk. Results We found that the susceptibility haplotype in our European sample had increased from 2 to 50 percent very recently in the European population, and to almost the same extent in the Asian population. The cause of this increase is unknown. The maximal proportion of overall genetic variation due to differences between groups for Europeans versus Africans and Europeans versus Asians (the Fst value closely matched the putative location of the susceptibility variant as judged from haplotype-based association mapping. Conclusion The combined observation that a common haplotype causing an increased risk of cancer in Europeans and a high differentiation between human populations is highly unusual and suggests a causal relationship with a recent increase in Europeans caused either by genetic drift overruling selection against the susceptibility variant or a positive selection for the same haplotype. The data does not allow us to distinguish between these two scenarios. The analysis suggests that the region is not involved in cancer risk in Africans and that the susceptibility variants may be more finely mapped in Asian populations.

  10. A novel partial deletion of the Y chromosome azoospermia factor c region is caused by non-homologous recombination between palindromes and may be associated with increased sperm counts

    NARCIS (Netherlands)

    M.J. Noordam; S.K.M. van Daalen; S.E. Hovingh; C.M. Korver; F. van der Veen; S. Repping

    2011-01-01

    BACKGROUND: The male-specific region of the human Y chromosome (MSY) contains multiple testis-specific genes. Most deletions in the MSY lead to inadequate or absent sperm production. Nearly all deletions occur via homologous recombination between amplicons. Previously, we identified two P5/distal-P1

  11. Synthetic chromosomes.

    Science.gov (United States)

    Schindler, Daniel; Waldminghaus, Torsten

    2015-11-01

    What a living organism looks like and how it works and what are its components-all this is encoded on DNA, the genetic blueprint. Consequently, the way to change an organism is to change its genetic information. Since the first pieces of recombinant DNA have been used to transform cells in the 1970s, this approach has been enormously extended. Bigger and bigger parts of the genetic information have been exchanged or added over the years. Now we are at a point where the construction of entire chromosomes becomes a reachable goal and first examples appear. This development leads to fundamental new questions, for example, about what is possible and desirable to build or what construction rules one needs to follow when building synthetic chromosomes. Here we review the recent progress in the field, discuss current challenges and speculate on the appearance of future synthetic chromosomes.

  12. Sequential Turnovers of Sex Chromosomes in African Clawed Frogs (Xenopus Suggest Some Genomic Regions Are Good at Sex Determination

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    Benjamin L. S. Furman

    2016-11-01

    Full Text Available Sexual differentiation is fundamentally important for reproduction, yet the genetic triggers of this developmental process can vary, even between closely related species. Recent studies have uncovered, for example, variation in the genetic triggers for sexual differentiation within and between species of African clawed frogs (genus Xenopus. Here, we extend these discoveries by demonstrating that yet another sex determination system exists in Xenopus, specifically in the species Xenopus borealis. This system evolved recently in an ancestor of X. borealis that had the same sex determination system as X. laevis, a system which itself is newly evolved. Strikingly, the genomic region carrying the sex determination factor in X. borealis is homologous to that of therian mammals, including humans. Our results offer insights into how the genetic underpinnings of conserved phenotypes evolve, and suggest an important role for cooption of genetic building blocks with conserved developmental roles.

  13. Localization of the human RNA polymerase I transcription factor gene (UBTF) to the D17S183 locus on chromosome 17q21 and construction of a long-range restriction map of the region

    Energy Technology Data Exchange (ETDEWEB)

    Jones, K.A.; Black, D.M.; Griffiths, B.L.; Solomon, E. [Somatic Cell Genetics Lab., London (United Kingdom)

    1995-12-10

    Human upstream binding factor (hUBF) is a sequence-specific DNA-binding protein that is essential for the activation of human 18s and 28s rRNA gene transcription. We have isolated and localized the gene (UBTF) encoding hUBF to the D17S183 locus on chromosome 17q21 by analyzing a cosmid from the region and carrying out Southern analysis on a previously constructed chromosome 17 somatic cell hybrid mapping panel using a probe from the hUBF cDNA. Confirmation of its location at this region was obtained from the results of pulsed-field gel electrophoresis analysis of genomic DNA using the hUBF cDNA and other probes from the region. These data also enabled the construction of a long-range restriction map of the region. 13 refs., 2 figs., 1 tab.

  14. Chromosomal aberration frequencies determined by conventional methods: Parallel increases over time in the region of a petrochemical industry and throughout the Czech Republic.

    Science.gov (United States)

    Sram, Radim J; Rössner, Pavel; Beskid, Olena; Bavorova, Hana; Ocadlikova, Dana; Solansky, Ivo; Albertini, Richard J

    2007-03-20

    The rationale for cytogenetic monitoring to determine if safe maximum allowable concentrations (MAC) of genotoxic chemicals are being maintained in a workplace is that exposure levels that do not increase chromosomal aberration frequencies are without harmful effects. Such monitoring, widely used in occupational health programs in the Czech Republic (CR), includes workers exposed to 1,3-butadiene (BD) or other chemicals. Studies of BD exposed workers in the years 1992, 1993, 1994, 1998, and 2004 compared mean frequencies of cells carrying chromosomal aberrations (frequency of aberrant cells=%AB.C.) in exposed workers with those in non-exposed matched controls in the same plant or in other individuals living in the region of the same petrochemical industry. Workers potentially exposed to acrylonitrile at this site were also evaluated in 2000, along with another unexposed matched control group. The %AB.C. values of exposed workers and their controls were also compared with reference values determined for normal individuals (ages 20-59 years) throughout the CR. Substantial discrepancies were noted between subjects in the region of the petrochemical industry (exposed workers and controls) for the years 2000 and 2004 and the reference CR-wide normal values that had been determined during an earlier time period. The matched non-exposed controls at the petrochemical industry site showed a mean %AB.C. value of 1.56+/-1.23% (N=25) in 1998; this rose to a mean of 2.65+/-2.29% (N=33) in 2000. In 2004, values for non-exposed matched controls at the industry site were 2.64+/-1.75% for males (N=25) and 2.38+/-1.74% (N=26) for females. However, the earlier determined CR-wide %AB.C. mean reference values for normal individuals were 1.77+/-1.16% (N=1305) for the interval 1977-1988 and 1.45+/-1.17% (N=2140) for the interval 1991-1999. As both reference values are substantially lower than those determined in 2000 and 2004 for the non-exposed matched controls at the petrochemical

  15. Refined genetic mapping of autosomal dominant retinitis pigmentosa locus RP18 reduces the critical region to 2 cM between D1S442 and D1S2858 on chromosome 1q.

    Science.gov (United States)

    Xu, S Y; Rosenberg, T; Gal, A

    1998-04-01

    Linkage analysis was performed on a large Danish family to refine the position of RP18, the locus for autosomal dominant retinitis pigmentosa, mapped previously between D1S534 and D1S305 in chromosome 1p13-q21. We genotyped the family members for five microsatellite-type DNA polymorphisms and mapped RP18 between D1S422 and D1S2858 to a region of less than 2 cM. No obvious candidate gene has yet been assigned to the chromosomal interval defined here.

  16. Adipose and muscle tissue gene expression of two genes (NCAPG and LCORL located in a chromosomal region associated with cattle feed intake and gain.

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    Amanda K Lindholm-Perry

    Full Text Available A region on bovine chromosome 6 has been implicated in cattle birth weight, growth, and length. Non-SMC conodensin I complex subunit G (NCAPG and ligand dependent nuclear receptor corepressor-like protein (LCORL are positional candidate genes within this region. Previously identified genetic markers in both genes were associated with average daily gain (ADG and average daily feed intake (ADFI in a crossbred population of beef steers. These markers were also associated with hot carcass weight, ribeye area and adjusted fat thickness suggesting that they may have a role in lean muscle growth and/or fat deposition. The purpose of this study was to determine whether the transcript abundance of either of these genes in cattle adipose and muscle tissue was associated with variation in feed intake and average daily gain phenotypes. Transcript abundance for NCAPG and LCORL in adipose and muscle tissue was measured in heifers (adipose only, cows and steers using real-time polymerase chain reaction. In the adipose tissue from cows and heifers, a negative correlation between LCORL transcript abundance and ADFI were detected (P = 0.05. In the muscle tissue from cows, transcript abundance of NCAPG was associated with ADG (r = 0.26; P = 0.009. A positive correlation between LCORL transcript abundance from muscle tissue of steers and ADFI was detected (P = 0.04. LCORL protein levels in the muscle of steers were investigated and were associated with ADFI (P = 0.01. These data support our earlier genetic associations with ADFI and ADG within this region and represent the potential for biological activity of these genes in the muscle and adipose tissues of beef cattle; however, they also suggest that sex, age and/or nutrition-specific interactions may affect the expression of NCAPG and LCORL in these tissues.

  17. Four chromosomal breakpoints and four new probes mark out a 10-cM region encompassing the fragile-X locus (FRAXA).

    Science.gov (United States)

    Rousseau, F; Vincent, A; Rivella, S; Heitz, D; Triboli, C; Maestrini, E; Warren, S T; Suthers, G K; Goodfellow, P; Mandel, J L

    1991-01-01

    We report the validation and use of a cell hybrid panel which allowed us a rapid physical localization of new DNA probes in the vicinity of the fragile-X locus (FRAXA). Seven regions are defined by this panel, two of which lie between DXS369 and DXS296, until now the closest genetic markers that flank FRAXA. Of those two interesting regions, one is just distal to DXS369 and defined by probe 2-71 (DXS476), which is not polymorphic. The next one contains probes St677 (DXS463) and 2-34 (DXS477), which are within 130 kb and both detect TaqI RFLPs. The combined informativeness of these two probes is 30%. We cloned from an irradiation-reduced hybrid line another new polymorphic probe, Do33 (DXS465; 42% heterozygosity). This probe maps to the DXS296 region, proximal to a chromosomal breakpoint that corresponds to the Hunter syndrome locus (IDS). The physical order is thus Cen-DXS369-DXS476-(DXS463,DXS477)-(DXS296, DXS465)-IDS-DXS304-tel. We performed a linkage analysis for five of these markers in both the Centre d'Etude du Polymorphisme Humain families and in a large set of fragile-X families. This establishes that DXS296 is distal to FRAXA. The relative position of DXS463 and DXS477 with respect to FRAXA remains uncertain, but our results place them genetically halfway between DXS369 and DXS304. Thus the DXS463-DXS477 cluster defines presently either the closest proximal or the closest distal polymorphic marker with respect to FRAXA. The three new polymorphic probes described here have a combined heterozygosity of 60% and represent a major improvement for genetic analysis of fragile-X families, in particular for diagnostic applications.

  18. Adipose and muscle tissue gene expression of two genes (NCAPG and LCORL) located in a chromosomal region associated with cattle feed intake and gain.

    Science.gov (United States)

    Lindholm-Perry, Amanda K; Kuehn, Larry A; Oliver, William T; Sexten, Andrea K; Miles, Jeremy R; Rempel, Lea A; Cushman, Robert A; Freetly, Harvey C

    2013-01-01

    A region on bovine chromosome 6 has been implicated in cattle birth weight, growth, and length. Non-SMC conodensin I complex subunit G (NCAPG) and ligand dependent nuclear receptor corepressor-like protein (LCORL) are positional candidate genes within this region. Previously identified genetic markers in both genes were associated with average daily gain (ADG) and average daily feed intake (ADFI) in a crossbred population of beef steers. These markers were also associated with hot carcass weight, ribeye area and adjusted fat thickness suggesting that they may have a role in lean muscle growth and/or fat deposition. The purpose of this study was to determine whether the transcript abundance of either of these genes in cattle adipose and muscle tissue was associated with variation in feed intake and average daily gain phenotypes. Transcript abundance for NCAPG and LCORL in adipose and muscle tissue was measured in heifers (adipose only), cows and steers using real-time polymerase chain reaction. In the adipose tissue from cows and heifers, a negative correlation between LCORL transcript abundance and ADFI were detected (P = 0.05). In the muscle tissue from cows, transcript abundance of NCAPG was associated with ADG (r = 0.26; P = 0.009). A positive correlation between LCORL transcript abundance from muscle tissue of steers and ADFI was detected (P = 0.04). LCORL protein levels in the muscle of steers were investigated and were associated with ADFI (P = 0.01). These data support our earlier genetic associations with ADFI and ADG within this region and represent the potential for biological activity of these genes in the muscle and adipose tissues of beef cattle; however, they also suggest that sex, age and/or nutrition-specific interactions may affect the expression of NCAPG and LCORL in these tissues.

  19. Ocular expression and distribution of products of the POAG-associated chromosome 9p21 gene region.

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    Glyn Chidlow

    Full Text Available It has recently been shown that there are highly significant associations for common single nucleotide polymorphisms (SNPs near the CDKN2B-AS1 gene region at the 9p21 locus with primary open angle glaucoma (POAG, a leading cause of irreversible blindness. This gene region houses the CDKN2B/p15(INK4B , CDKN2A/p16(INK4A and p14ARF (rat equivalent, p19(ARF tumour suppressor genes and is adjacent to the S-methyl-5'-thioadenosine phosphorylase (MTAP gene. In order to understand the ocular function of these genes and, therefore, how they may be involved in the pathogenesis of POAG, we studied the distribution patterns of each of their products within human and rat ocular tissues. MTAP mRNA was detected in the rat retina and optic nerve and its protein product was localised to the corneal epithelium, trabecular meshwork and retinal glial cells in both human and rat eyes. There was a very low level of p16(INK4A mRNA present within the rat retina and slightly more in the optic nerve, although no protein product could be detected in either rat or human eyes with any of the antibodies tested. P19(ARF mRNA was likewise only present at very low levels in rat retina and slightly higher levels in the optic nerve. However, no unambiguous evidence was found to indicate expression of specific P19(ARF/p14(ARF proteins in either rat or human eyes, respectively. In contrast, p15(INK4B mRNA was detected in much higher amounts in both retina and optic nerve compared with the other genes under analysis. Moreover, p15(INK4B protein was clearly localised to the retinal inner nuclear and ganglion cell layers and the corneal epithelium and trabecular meshwork in rat and human eyes. The presented data provide the basis for future studies that can explore the roles that these gene products may play in the pathogenesis of glaucoma and other models of optic nerve damage.

  20. Assignment of the human gene for the water channel of renal collecting duct Aquaporin 2 (AQP2) to chromosome 12 region q12-->q13

    NARCIS (Netherlands)

    Deen, P M; Weghuis, D O; Sinke, R J; Geurts van Kessel, A; Wieringa, B; van Os, C H

    1994-01-01

    The chromosomal localization of the gene encoding Aquaporin 2 (previously called WCH-CD), which acts as a water channel in the collecting tubules of the kidney, was determined. Southern blot hybridizations of chromosomal DNA from a panel of 25 different human-rodent hybrid cell lines assigned AQP2 t

  1. Editorial: X-chromosome-linked Kallmann's syndrome: Pathology at the molecular level

    Energy Technology Data Exchange (ETDEWEB)

    Prager, D.; Braunstein, G.D. (Cedars-Sinai Medical Center, Los Angeles, CA (United States))

    1993-04-01

    Kallmann's syndrome or olfactogenital dysplasia refers to a disorder characterized by hypogonadotropic hypogonadism and anosmia or hyposmia which can occur sporadically or in a familial setting. Originally described in 1856, the first familial cases were reported by Kallmann et al., in 1944. Based on segregation analysis of multiple families, three modes of transmission have been documented: X-linked, autosomal dominant with variable penetrance, and autosomal recessive. Kallmann's syndrome occurs in less than 1 in 10,000 male births, with a 5-fold excess of affected males to females, suggesting that the X-linked form is the most frequent. By genetic linkage analysis the X-linked form of Kallmann's syndrome was localized to Xp22.3. This was confirmed by the description of patients with contiguous gene syndromes due to deletions of various portions of the distal short arm of the X-chromosome. Such patients present with complex phenotypes characterized by a combination of Kallmann's syndrome with X-linked icthyosis due to steroid sulfatase deficiency, chondrodysplasia punctata, short stature, and mental retardation. DNA analysis has identified and mapped the genes responsible for these disorders. 10 refs., 1 fig., 1 tab.

  2. A yeast artificial chromosome contig that spans the RB1-D13S31 interval on human chromosome 13 and encompasses the frequently deleted region in B-cell chronic lymphocytic leukemia

    NARCIS (Netherlands)

    Hawthorn, L; Roberts, T; Verlind, E; Kooy, RF; Cowell, JK

    1995-01-01

    Abnormalities involving chromosome 13 have been reported as the only cytogenetic change in B-cell chronic lymphocytic leukemia (BCLL). Deletions are the most common cytogenetic abnormality and always involve 13q14, but when translocations are seen, the consistent breakpoint is always in 13q14. It is

  3. Investigation of LDHA and COPB1 as candidate genes for muscle development in the MYOD1 region of pig chromosome 2.

    Science.gov (United States)

    Qiu, Haifeng; Xu, Xuewen; Fan, Bing; Rothschild, Max F; Martin, Yerle; Liu, Bang

    2010-01-01

    Porcine MYOD1 gene has been mapped to swine chromosome (SSC) 2p14-p17, which is involved in the regulation of the proliferation and differentiation of skeletal muscle cells. The LDHA (lactate dehydrogenase A) and COPB1 (coatomer protein complex, subunit beta 1) genes, which map close to MYOD1, are involved in energy metabolism and protein transport processes. Both genes might play important roles in muscle development. However, little is known about the porcine LDHA and COPB1 genes. In the present study, the full-length cDNA of these two genes were cloned. The mapping results demonstrated that porcine LDHA and COPB1 were all mapped to SSC 2p14-p17. In this region, there are several QTL for growth and carcass traits, including average backfat thickness, lean and fat percentage. The RT-PCR results revealed that both LDHA and COPB1 were highly expressed in porcine skeletal muscle tissues, implying their potential regulatory function of muscle development. LDHA and COPB1 were then mapped to the region and multipoint analyses generated a best sex-averaged map order of each gene between linked markers: MYOD1_75.2 cM _LDHA_79 cM _CSRP3_83.8 cM _TEF-1_86.5 cM _COPB1_90 cM. Association analyses revealed that the substitution of c.423A>G had a significant effect on average daily gain on test, average backfat thickness (BFT), loin muscle area, lumbar BFT, marbling score, tenth rib BFT, average drip loss and fiber type II ratio. The substitution of c.3096C>T had a significant effect on average BFT, lumbar BFT, tenth rib BFT, carcass weight and last rib BFT. Interestingly, both SNPs were all associated with average BFT, lumbar BFT and tenth rib BFT.

  4. Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk.

    Science.gov (United States)

    Lin, Wei-Yu; Camp, Nicola J; Ghoussaini, Maya; Beesley, Jonathan; Michailidou, Kyriaki; Hopper, John L; Apicella, Carmel; Southey, Melissa C; Stone, Jennifer; Schmidt, Marjanka K; Broeks, Annegien; Van't Veer, Laura J; Th Rutgers, Emiel J; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Fasching, Peter A; Haeberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Peto, Julian; Dos-Santos-Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Sawyer, Elinor J; Cheng, Timothy; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marmé, Frederik; Surowy, Harald M; Burwinkel, Barbara; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Mulot, Claire; Bojesen, Stig E; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Benitez, Javier; Zamora, M Pilar; Arias Perez, Jose Ignacio; Menéndez, Primitiva; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Alvarez, Nuria; Herrero, Daniel; Anton-Culver, Hoda; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Lichtner, Peter; Schmutzler, Rita K; Müller-Myhsok, Bertram; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; Nevanlinna, Heli; Aittomäki, Kristiina; Blomqvist, Carl; Khan, Sofia; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Horio, Akiyo; Bogdanova, Natalia V; Antonenkova, Natalia N; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Wu, Anna H; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Neven, Patrick; Wauters, Els; Wildiers, Hans; Lambrechts, Diether; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Bonanni, Bernardo; Couch, Fergus J; Wang, Xianshu; Vachon, Celine; Purrington, Kristen; Giles, Graham G; Milne, Roger L; Mclean, Catriona; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Teo, Soo Hwang; Yip, Cheng Har; Hassan, Norhashimah; Vithana, Eranga Nishanthie; Kristensen, Vessela; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha J; Long, Jirong; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; Van Asperen, Christi J; García-Closas, Montserrat; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Brand, Judith S; Hooning, Maartje J; Hollestelle, Antoinette; Van Den Ouweland, Ans M W; Jager, Agnes; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Cross, Simon S; Reed, Malcolm W R; Blot, William; Signorello, Lisa B; Cai, Qiuyin; Pharoah, Paul D P; Perkins, Barbara; Shah, Mitul; Blows, Fiona M; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Hartman, Mikael; Miao, Hui; Chia, Kee Seng; Putti, Thomas Choudary; Hamann, Ute; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Maranian, Mel; Healey, Catherine S; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; Mckay, James; Slager, Susan; Toland, Amanda E; Yannoukakos, Drakoulis; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Ding, Shian-Ling; Ashworth, Alan; Jones, Michael; Orr, Nick; Swerdlow, Anthony J; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel F; Bui, Quang M; Chanock, Stephen J; Hunter, David J; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Muranen, Taru A; Heikkinen, Tuomas; Irwanto, Astrid; Rahman, Nazneen; Turnbull, Clare A; Waisfisz, Quinten; Meijers-Heijboer, Hanne E J; Adank, Muriel A; Van Der Luijt, Rob B; Hall, Per; Chenevix-Trench, Georgia; Dunning, Alison; Easton, Douglas F; Cox, Angela

    2015-01-01

    Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide polymorphisms (SNPs) spanning a 1 Mb region around CASP8 were genotyped in 46 450 breast cancer cases and 42 600 controls of European origin from 41 studies participating in the BCAC as part of a custom genotyping array experiment (iCOGS). Missing genotypes and SNPs were imputed and, after quality exclusions, 501 typed and 1232 imputed SNPs were included in logistic regression models adjusting for study and ancestry principal components. The SNPs retained in the final model were investigated further in data from nine genome-wide association studies (GWAS) comprising in total 10 052 case and 12 575 control subjects. The most significant association signal observed in European subjects was for the imputed intronic SNP rs1830298 in ALS2CR12 (telomeric to CASP8), with per allele odds ratio and 95% confidence interval [OR (95% confidence interval, CI)] for the minor allele of 1.05 (1.03-1.07), P = 1 × 10(-5). Three additional independent signals from intronic SNPs were identified, in CASP8 (rs36043647), ALS2CR11 (rs59278883) and CFLAR (rs7558475). The association with rs1830298 was replicated in the imputed results from the combined GWAS (P = 3 × 10(-6)), yielding a combined OR (95% CI) of 1.06 (1.04-1.08), P = 1 × 10(-9). Analyses of gene expression associations in peripheral blood and normal breast tissue indicate that CASP8 might be the target gene, suggesting a mechanism involving apoptosis.

  5. Deletion of Chromosomal Region 8p21 Confers Resistance to Bortezomib and Is Associated with Upregulated Decoy TRAIL Receptor Expression in Patients with Multiple Myeloma.

    Directory of Open Access Journals (Sweden)

    Adil Doganay Duru

    Full Text Available Loss of the chromosomal region 8p21 negatively effects survival in patients with multiple myeloma (MM that undergo autologous stem cell transplantation (ASCT. In this study, we aimed to identify the immunological and molecular consequences of del(8(p21 with regards to treatment response and bortezomib resistance. In patients receiving bortezomib as a single first line agent without any high-dose therapy, we have observed that patients with del(8(p21 responded poorly to bortezomib with 50% showing no response while patients without the deletion had a response rate of 90%. In vitro analysis revealed a higher resistance to bortezomib possibly due to an altered gene expression profile caused by del(8(p21 including genes such as TRAIL-R4, CCDC25, RHOBTB2, PTK2B, SCARA3, MYC, BCL2 and TP53. Furthermore, while bortezomib sensitized MM cells without del(8(p21 to TRAIL/APO2L mediated apoptosis, in cells with del(8(p21 bortezomib failed to upregulate the pro-apoptotic death receptors TRAIL-R1 and TRAIL-R2 which are located on the 8p21 region. Also expressing higher levels of the decoy death receptor TRAIL-R4, these cells were largely resistant to TRAIL/APO2L mediated apoptosis. Corroborating the clinical outcome of the patients, our data provides a potential explanation regarding the poor response of MM patients with del(8(p21 to bortezomib treatment. Furthermore, our clinical analysis suggests that including immunomodulatory agents such as Lenalidomide in the treatment regimen may help to overcome this negative effect, providing an alternative consideration in treatment planning of MM patients with del(8(p21.

  6. Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk

    Science.gov (United States)

    Lin, Wei-Yu; Camp, Nicola J.; Ghoussaini, Maya; Beesley, Jonathan; Michailidou, Kyriaki; Hopper, John L.; Apicella, Carmel; Southey, Melissa C.; Stone, Jennifer; Schmidt, Marjanka K.; Broeks, Annegien; Van't Veer, Laura J.; Th Rutgers, Emiel J.; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Fasching, Peter A.; Haeberle, Lothar; Ekici, Arif B.; Beckmann, Matthias W.; Peto, Julian; Dos-Santos-Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Sawyer, Elinor J.; Cheng, Timothy; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Marmé, Frederik; Surowy, Harald M.; Burwinkel, Barbara; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Mulot, Claire; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Benitez, Javier; Zamora, M. Pilar; Arias Perez, Jose Ignacio; Menéndez, Primitiva; González-Neira, Anna; Pita, Guillermo; Alonso, M. Rosario; Álvarez, Nuria; Herrero, Daniel; Anton-Culver, Hoda; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Lichtner, Peter; Schmutzler, Rita K.; Müller-Myhsok, Bertram; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Nevanlinna, Heli; Aittomäki, Kristiina; Blomqvist, Carl; Khan, Sofia; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Horio, Akiyo; Bogdanova, Natalia V.; Antonenkova, Natalia N.; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Wu, Anna H.; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O.; Neven, Patrick; Wauters, Els; Wildiers, Hans; Lambrechts, Diether; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Bonanni, Bernardo; Couch, Fergus J.; Wang, Xianshu; Vachon, Celine; Purrington, Kristen; Giles, Graham G.; Milne, Roger L.; Mclean, Catriona; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Teo, Soo Hwang; Yip, Cheng Har; Hassan, Norhashimah; Vithana, Eranga Nishanthie; Kristensen, Vessela; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha J.; Long, Jirong; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Robert A.E.M.; Seynaeve, Caroline; Van Asperen, Christi J.; García-Closas, Montserrat; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Brand, Judith S.; Hooning, Maartje J.; Hollestelle, Antoinette; Van Den Ouweland, Ans M.W.; Jager, Agnes; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Cross, Simon S.; Reed, Malcolm W. R.; Blot, William; Signorello, Lisa B.; Cai, Qiuyin; Pharoah, Paul D.P.; Perkins, Barbara; Shah, Mitul; Blows, Fiona M.; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Hartman, Mikael; Miao, Hui; Chia, Kee Seng; Putti, Thomas Choudary; Hamann, Ute; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Maranian, Mel; Healey, Catherine S.; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; Mckay, James; Slager, Susan; Toland, Amanda E.; Yannoukakos, Drakoulis; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Ding, Shian-ling; Ashworth, Alan; Jones, Michael; Orr, Nick; Swerdlow, Anthony J; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel F.; Bui, Quang M.; Chanock, Stephen J.; Hunter, David J.; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Muranen, Taru A.; Heikkinen, Tuomas; Irwanto, Astrid; Rahman, Nazneen; Turnbull, Clare A.; Waisfisz, Quinten; Meijers-Heijboer, Hanne E. J.; Adank, Muriel A.; Van Der Luijt, Rob B.; Hall, Per; Chenevix-Trench, Georgia; Dunning, Alison; Easton, Douglas F.; Cox, Angela

    2015-01-01

    Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide polymorphisms (SNPs) spanning a 1 Mb region around CASP8 were genotyped in 46 450 breast cancer cases and 42 600 controls of European origin from 41 studies participating in the BCAC as part of a custom genotyping array experiment (iCOGS). Missing genotypes and SNPs were imputed and, after quality exclusions, 501 typed and 1232 imputed SNPs were included in logistic regression models adjusting for study and ancestry principal components. The SNPs retained in the final model were investigated further in data from nine genome-wide association studies (GWAS) comprising in total 10 052 case and 12 575 control subjects. The most significant association signal observed in European subjects was for the imputed intronic SNP rs1830298 in ALS2CR12 (telomeric to CASP8), with per allele odds ratio and 95% confidence interval [OR (95% confidence interval, CI)] for the minor allele of 1.05 (1.03–1.07), P = 1 × 10−5. Three additional independent signals from intronic SNPs were identified, in CASP8 (rs36043647), ALS2CR11 (rs59278883) and CFLAR (rs7558475). The association with rs1830298 was replicated in the imputed results from the combined GWAS (P = 3 × 10−6), yielding a combined OR (95% CI) of 1.06 (1.04–1.08), P = 1 × 10−9. Analyses of gene expression associations in peripheral blood and normal breast tissue indicate that CASP8 might be the target gene, suggesting a mechanism involving apoptosis. PMID:25168388

  7. A chromosome 5q31.1 locus associates with tuberculin skin test reactivity in HIV-positive individuals from tuberculosis hyper-endemic regions in east Africa.

    Science.gov (United States)

    Sobota, Rafal S; Stein, Catherine M; Kodaman, Nuri; Maro, Isaac; Wieland-Alter, Wendy; Igo, Robert P; Magohe, Albert; Malone, LaShaunda L; Chervenak, Keith; Hall, Noemi B; Matee, Mecky; Mayanja-Kizza, Harriet; Joloba, Moses; Moore, Jason H; Scott, William K; Lahey, Timothy; Boom, W Henry; von Reyn, C Fordham; Williams, Scott M; Sirugo, Giorgio

    2017-06-01

    One in three people has been infected with Mycobacterium tuberculosis (MTB), and the risk for MTB infection in HIV-infected individuals is even higher. We hypothesized that HIV-positive individuals living in tuberculosis-endemic regions who do not get infected by Mycobacterium tuberculosis are genetically resistant. Using an "experiment of nature" design that proved successful in our previous work, we performed a genome-wide association study of tuberculin skin test positivity using 469 HIV-positive patients from prospective study cohorts of tuberculosis from Tanzania and Uganda to identify genetic loci associated with MTB infection in the context of HIV-infection. Among these individuals, 244 tested were tuberculin skin test (TST) positive either at enrollment or during the >8 year follow up, while 225 were not. We identified a genome-wide significant association between a dominant model of rs877356 and binary TST status in the combined cohort (Odds ratio = 0.2671, p = 1.22x10-8). Association was replicated with similar significance when examining TST induration as a continuous trait. The variant lies in the 5q31.1 region, 57kb downstream from IL9. Two-locus analyses of association of variants near rs877356 showed a haplotype comprised of rs877356 and an IL9 missense variant, rs2069885, had the most significant association (p = 1.59x10-12). We also replicated previously linked loci on chromosomes 2, 5, and 11. IL9 is a cytokine produced by mast cells and TH2 cells during inflammatory responses, providing a possible link between airway inflammation and protection from MTB infection. Our results indicate that studying uninfected, HIV-positive participants with extensive exposure increases the power to detect associations in complex infectious disease.

  8. Chromosomal rearrangement interferes with meiotic X chromosome inactivation.

    Science.gov (United States)

    Homolka, David; Ivanek, Robert; Capkova, Jana; Jansa, Petr; Forejt, Jiri

    2007-10-01

    Heterozygosity for certain mouse and human chromosomal rearrangements is characterized by the incomplete meiotic synapsis of rearranged chromosomes, by their colocalization with the XY body in primary spermatocytes, and by male-limited sterility. Previously, we argued that such X-autosomal associations could interfere with meiotic sex chromosome inactivation. Recently, supporting evidence has reported modifications of histones in rearranged chromosomes by a process called the meiotic silencing of unsynapsed chromatin (MSUC). Here, we report on the transcriptional down-regulation of genes within the unsynapsed region of the rearranged mouse chromosome 17, and on the subsequent disturbance of X chromosome inactivation. The partial transcriptional suppression of genes in the unsynapsed chromatin was most prominent prior to the mid-pachytene stage of primary spermatocytes. Later, during the mid-late pachytene, the rearranged autosomes colocalized with the XY body, and the X chromosome failed to undergo proper transcriptional silencing. Our findings provide direct evidence on the MSUC acting at the mRNA level, and implicate that autosomal asynapsis in meiosis may cause male sterility by interfering with meiotic sex chromosome inactivation.

  9. Improving global and regional resolution of male lineage differentiation by simple single-copy Y-chromosomal short tandem repeat polymorphisms

    Science.gov (United States)

    Vermeulen, Mark; Wollstein, Andreas; van der Gaag, Kristiaan; Lao, Oscar; Xue, Yali; Wang, Qiuju; Roewer, Lutz; Knoblauch, Hans; Tyler-Smith, Chris; de Knijff, Peter; Kayser, Manfred

    2012-01-01

    We analysed 67 short tandem repeat polymorphisms from the non-recombining part of the Y-chromosome (Y-STRs), including 49 rarely-studied simple single-copy (ss)Y-STRs and 18 widely-used Y-STRs, in 590 males from 51 populations belonging to 8 worldwide regions (HGDP-CEPH panel). Although autosomal DNA profiling provided no evidence for close relationship, we found 18 Y-STR haplotypes (defined by 67 Y-STRs) that were shared by two to five men in 13 worldwide populations, revealing high and widespread levels of cryptic male relatedness. Maximal (95.9%) haplotype resolution was achieved with the best 25 out of 67 Y-STRs in the global dataset, and with the best 3-16 markers in regional datasets (89.6-100% resolution). From the 49 rarely-studied ssY-STRs, the 25 most informative markers were sufficient to reach the highest possible male lineage differentiation in the global (92.2% resolution), and 3-15 markers in the regional datasets (85.4-100%). Considerably lower haplotype resolutions were obtained with the three commonly-used Y-STR sets (Minimal Haplotype, PowerPlex Y®, and AmpFlSTR® Yfiler®). Six ssY-STRs (DYS481, DYS533, DYS549, DYS570, DYS576 and DYS643) were most informative to supplement the existing Y-STR kits for increasing haplotype resolution, or – together with additional ssY-STRs - as a new set for maximizing male lineage differentiation. Mutation rates of the 49 ssY-STRs were estimated from 403 meiotic transfers in deep-rooted pedigrees, and ranged from ~4.8×10−4 for 31 ssY-STRs with no mutations observed to 1.3×10−2 and 1.5×10−2 for DYS570 and DYS576, respectively, the latter representing the highest mutation rates reported for human Y-STRs so far. Our findings thus demonstrate that ssY-STRs are useful for maximizing global and regional resolution of male lineages, either as a new set, or when added to commonly-used Y-STR sets, and support their application to forensic, genealogical and anthropological studies. PMID:19647704

  10. Chromosome painting of Z and W sex chromosomes in Characidium (Characiformes, Crenuchidae).

    Science.gov (United States)

    Pazian, Marlon F; Shimabukuro-Dias, Cristiane Kioko; Pansonato-Alves, José Carlos; Oliveira, Claudio; Foresti, Fausto

    2013-03-01

    Some species of the genus Characidium have heteromorphic ZZ/ZW sex chromosomes with a totally heterochromatic W chromosome. Methods for chromosome microdissection associated with chromosome painting have become important tools for cytogenetic studies in Neotropical fish. In Characidium cf. fasciatum, the Z chromosome contains a pericentromeric heterochromatin block, whereas the W chromosome is completely heterochromatic. Therefore, a probe was produced from the W chromosome through microdissection and degenerate oligonucleotide-primed polymerase chain reaction amplification. FISH was performed using the W probe on the chromosomes of specimens of this species. This revealed expressive marks in the pericentromeric region of the Z chromosome as well as a completely painted W chromosome. When applying the same probe on chromosome preparations of C. cf. gomesi and Characidium sp., a pattern similar to C. cf. fasciatum was found, while C. cf. zebra, C. cf. lagosantense and Crenuchus spilurus species showed no hybridization signals. Structural changes in the chromosomes of an ancestral sexual system in the group that includes the species C. cf. gomesi, C. cf. fasciatum and Characidium sp., could have contributed to the process of speciation and could represent a causal mechanism of chromosomal diversification in this group. The heterochromatinization process possibly began in homomorphic and homologous chromosomes of an ancestral form, and this process could have given rise to the current patterns found in the species with sex chromosome heteromorphism.

  11. Chromosome Analysis

    Science.gov (United States)

    1998-01-01

    Perceptive Scientific Instruments, Inc., provides the foundation for the Powergene line of chromosome analysis and molecular genetic instrumentation. This product employs image processing technology from NASA's Jet Propulsion Laboratory and image enhancement techniques from Johnson Space Center. Originally developed to send pictures back to earth from space probes, digital imaging techniques have been developed and refined for use in a variety of medical applications, including diagnosis of disease.

  12. RAG-dependent recombination at cryptic RSSs within TEL–AML1 t(12;21)(p13;q22) chromosomal translocation region

    OpenAIRE

    Numata, Masashi; Saito, Shoko; Nagata, Kyosuke

    2010-01-01

    The recombination activating gene (RAG) is a lymphoid-specific endonuclease involved in the V(D)J recombination. It has long been proposed that mis-targeting of RAG proteins is one of the factors contributing to lymphoid chromosomal translocation bearing authentic recombination signal sequences (RSSs) in immunoglobulin (Ig) and T cell receptor (TCR) gene loci or cryptic RSSs (cRSSs). However, it is unclear whether primary sequence-dependent targeting mistake involved in the chromosomal transl...

  13. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.

    OpenAIRE

    Wang, Zhaoming; Zhu, Bin; Zhang, Mingfeng; Parikh, Hemang; Jia, Jinping; Chung, Charles C.; Sampson, Joshua N.; Hoskins, Jason W; Hutchinson, Amy; Burdette, Laurie; Ibrahim, Abdisamad; Hautman, Christopher; Raj, Preethi S.; Abnet, Christian C.; Adjei, Andrew A.

    2014-01-01

    Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based...

  14. Kagami-Ogata syndrome: a clinically recognizable upd(14)pat and related disorder affecting the chromosome 14q32.2 imprinted region.

    Science.gov (United States)

    Ogata, Tsutomu; Kagami, Masayo

    2016-02-01

    Human chromosome 14q32.2 carries paternally expressed genes including DLK1 and RTL1, and maternally expressed genes including MEG3 and RTL1as, along with the germline-derived DLK1-MEG3 intergenic differentially methylated region (IG-DMR) and the postfertilization-derived MEG3-DMR. Consistent with this, paternal uniparental disomy 14 (upd(14)pat), and epimutations (hypermethylations) and microdeletions affecting the IG-DMR and/or the MEG3-DMR of maternal origin, result in a unique phenotype associated with characteristic face, a small bell-shaped thorax with coat-hanger appearance of the ribs, abdominal wall defects, placentomegaly and polyhydramnios. Recently, the name 'Kagami-Ogata syndrome' (KOS) has been approved for this clinically recognizable disorder. Here, we review the current knowledge about KOS. Important findings include the following: (1) the facial 'gestalt' and the increased coat-hanger angle constitute pathognomonic features from infancy through childhood/puberty; (2) the unmethylated IG-DMR and MEG3-DMR of maternal origin function as the imprinting control centers in the placenta and body respectively, with a hierarchical interaction regulated by the IG-DMR for the methylation pattern of the MEG3-DMR in the body; (3) RTL1 expression level becomes ~2.5 times increased in the absence of functional RTL1as-encoded microRNAs that act as a trans-acting repressor for RTL1; (4) excessive RTL1 expression and absent MEG expression constitute the primary underlying factor for the phenotypic development; and (5) upd(14)pat accounts for approximately two-thirds of KOS patients, and epimutations and microdeletions are identified with a similar frequency. Furthermore, we refer to diagnostic and therapeutic implications.

  15. Kagami–Ogata syndrome: a clinically recognizable upd(14)pat and related disorder affecting the chromosome 14q32.2 imprinted region

    Science.gov (United States)

    Ogata, Tsutomu; Kagami, Masayo

    2016-01-01

    Human chromosome 14q32.2 carries paternally expressed genes including DLK1 and RTL1, and maternally expressed genes including MEG3 and RTL1as, along with the germline-derived DLK1-MEG3 intergenic differentially methylated region (IG-DMR) and the postfertilization-derived MEG3-DMR. Consistent with this, paternal uniparental disomy 14 (upd(14)pat), and epimutations (hypermethylations) and microdeletions affecting the IG-DMR and/or the MEG3-DMR of maternal origin, result in a unique phenotype associated with characteristic face, a small bell-shaped thorax with coat-hanger appearance of the ribs, abdominal wall defects, placentomegaly and polyhydramnios. Recently, the name ‘Kagami–Ogata syndrome' (KOS) has been approved for this clinically recognizable disorder. Here, we review the current knowledge about KOS. Important findings include the following: (1) the facial ‘gestalt' and the increased coat-hanger angle constitute pathognomonic features from infancy through childhood/puberty; (2) the unmethylated IG-DMR and MEG3-DMR of maternal origin function as the imprinting control centers in the placenta and body respectively, with a hierarchical interaction regulated by the IG-DMR for the methylation pattern of the MEG3-DMR in the body; (3) RTL1 expression level becomes ~2.5 times increased in the absence of functional RTL1as-encoded microRNAs that act as a trans-acting repressor for RTL1; (4) excessive RTL1 expression and absent MEG expression constitute the primary underlying factor for the phenotypic development; and (5) upd(14)pat accounts for approximately two-thirds of KOS patients, and epimutations and microdeletions are identified with a similar frequency. Furthermore, we refer to diagnostic and therapeutic implications. PMID:26377239

  16. Single nucleotide polymorphisms in the REG-CTNNA2 region of chromosome 2 and NEIL3 associated with impulsivity in a Native American sample.

    Science.gov (United States)

    Ehlers, C L; Gizer, I R; Bizon, C; Slutske, W; Peng, Q; Schork, N J; Wilhelmsen, K C

    2016-07-01

    Impulsivity is a multi-faceted construct that, while characterized by a set of correlated dimensions, is centered around a core definition that involves acting suddenly in an unplanned manner without consideration for the consequences of such behavior. Several psychiatric disorders include impulsivity as a criterion, and thus it has been suggested that it may link a number of different behavioral disorders, including substance abuse. Native Americans (NA) experience some of the highest rates of substance abuse of all the US ethnic groups. The described analyses used data from a low-coverage whole genome sequence scan to conduct a genome-wide association study (GWAS) of an impulsivity phenotype in an American Indian community sample (n = 658). Demographic and clinical information were obtained using a semi-structured interview. Impulsivity was assessed using a scale derived from the Maudsley personality inventory that combines both novelty seeking and lack of planning items. The impulsivity score was tested for association with each variant adjusted for demographic variables, and corrected for ancestry and kinship, using emmax. Simulations were conducted to calculate empirical P-values. Genome-wide significant findings were observed for a variant 50-kb upstream from catenin cadherin-associated protein, alpha 2 (CTNNA2), a neuronal-specific catenin, in the REG gene cluster. A meta-analysis of GWAS had previously identified common variants in CTNNA2 as being associated with excitement seeking. A second locus upstream of nei endonuclease VIII-like 3 (NEIL3) on chromosome 4 also achieved genome-wide significance. The association between sequence variants in these regions suggests their potential roles in the genetic regulation of this phenotype in this population.

  17. The DYRK1A gene, encoded in chromosome 21 Down syndrome critical region, bridges between beta-amyloid production and tau phosphorylation in Alzheimer disease.

    Science.gov (United States)

    Kimura, Ryo; Kamino, Kouzin; Yamamoto, Mitsuko; Nuripa, Aidaralieva; Kida, Tomoyuki; Kazui, Hiroaki; Hashimoto, Ryota; Tanaka, Toshihisa; Kudo, Takashi; Yamagata, Hidehisa; Tabara, Yasuharu; Miki, Tetsuro; Akatsu, Hiroyasu; Kosaka, Kenji; Funakoshi, Eishi; Nishitomi, Kouhei; Sakaguchi, Gaku; Kato, Akira; Hattori, Hideyuki; Uema, Takeshi; Takeda, Masatoshi

    2007-01-01

    We scanned throughout chromosome 21 to assess genetic associations with late-onset Alzheimer disease (AD) using 374 Japanese patients and 375 population-based controls, because trisomy 21 is known to be associated with early deposition of beta-amyloid (Abeta) in the brain. Among 417 markers spanning 33 Mb, 22 markers showed associations with either the allele or the genotype frequency (P KCNJ6 genes. In logistic regression, the DYRK1A (dual-specificity tyrosine-regulated kinase 1A) gene, located in the Down syndrome critical region, showed the highest significance [OR = 2.99 (95% CI: 1.72-5.19), P = 0.001], whereas the RUNX1 gene showed a high odds ratio [OR = 23.3 (95% CI: 2.76-196.5), P = 0.038]. DYRK1A mRNA level in the hippocampus was significantly elevated in patients with AD when compared with pathological controls (P < 0.01). DYRK1A mRNA level was upregulated along with an increase in the Abeta-level in the brain of transgenic mice, overproducing Abeta at 9 months of age. In neuroblastoma cells, Abeta induced an increase in the DYRK1A transcript, which also led to tau phosphorylation at Thr212 under the overexpression of tau. Therefore, the upregulation of DYRK1A transcription results from Abeta loading, further leading to tau phosphorylation. Our result indicates that DYRK1A could be a key molecule bridging between beta-amyloid production and tau phosphorylation in AD.

  18. Sex-determining Region of Y Chromosome-related High-mobility-group Box 2 in Malignant Tumors: Current Opinions and Anticancer Therapy

    Institute of Scientific and Technical Information of China (English)

    Shi-Guang Cao; Zong-Juan Ming; Yu-Ping Zhang; Shuan-Ying Yang

    2015-01-01

    Objective:To gain insight into the mechanism by which sex-determining region of Y chromosome (SRY)-related high-mobility-group box 2 (SOX2) involved in carcinogenesis and cancer stem cells (CSCs).Data Sources:The data used in this review were mainly published in English from 2000 to present obtained from PubMed.The search terms were "SOX2," "cancer," "tumor" or "CSCs."Study Selection:Articles studying the mitochondria-related pathologic mechanism and treatment of glaucoma were selected and reviewed.Results:SOX2,a transcription factor that is the key in maintaining pluripotent properties of stem cells,is a member of SRy-related high-mobility group domain proteins.SOX2 participates in many biological processes,such as modulation of cell proliferation,regulation of cell death signaling,cell apoptosis,and most importantly,tumor formation and development.Although SOX2 has been implicated in the biology of various tumors and CSCs,the findings are highly controversial,and information regarding the underlying mechanism remains limited.Moreover,the mechanism by which SOX2 involved in carcinogenesis and tumor progression is rather unclear yet.Conclusions:Here,we review the important biological functions of SOX2 in different tumors and CSCs,and the function of SOX2 signaling in the pathobiology ofneoplasia,such as Wnt/β-catenin signaling pathway,Hippo signaling pathway,Survivin signaling pathway,PI3K/Akt signaling pathway,and so on.Targeting towards SOX2 may be an effective therapeutic strategy for cancer therapy.

  19. Deciphering evolutionary strata on plant sex chromosomes and fungal mating-type chromosomes through compositional segmentation.

    Science.gov (United States)

    Pandey, Ravi S; Azad, Rajeev K

    2016-03-01

    Sex chromosomes have evolved from a pair of homologous autosomes which differentiated into sex determination systems, such as XY or ZW system, as a consequence of successive recombination suppression between the gametologous chromosomes. Identifying the regions of recombination suppression, namely, the "evolutionary strata", is central to understanding the history and dynamics of sex chromosome evolution. Evolution of sex chromosomes as a consequence of serial recombination suppressions is well-studied for mammals and birds, but not for plants, although 48 dioecious plants have already been reported. Only two plants Silene latifolia and papaya have been studied until now for the presence of evolutionary strata on their X chromosomes, made possible by the sequencing of sex-linked genes on both the X and Y chromosomes, which is a requirement of all current methods that determine stratum structure based on the comparison of gametologous sex chromosomes. To circumvent this limitation and detect strata even if only the sequence of sex chromosome in the homogametic sex (i.e. X or Z chromosome) is available, we have developed an integrated segmentation and clustering method. In application to gene sequences on the papaya X chromosome and protein-coding sequences on the S. latifolia X chromosome, our method could decipher all known evolutionary strata, as reported by previous studies. Our method, after validating on known strata on the papaya and S. latifolia X chromosome, was applied to the chromosome 19 of Populus trichocarpa, an incipient sex chromosome, deciphering two, yet unknown, evolutionary strata. In addition, we applied this approach to the recently sequenced sex chromosome V of the brown alga Ectocarpus sp. that has a haploid sex determination system (UV system) recovering the sex determining and pseudoautosomal regions, and then to the mating-type chromosomes of an anther-smut fungus Microbotryum lychnidis-dioicae predicting five strata in the non

  20. Microdissection and chromosome painting of X and B chromosomes in Locusta migratoria.

    Science.gov (United States)

    Teruel, María; Cabrero, Josefa; Montiel, Eugenia E; Acosta, Manuel J; Sánchez, Antonio; Camacho, Juan Pedro M

    2009-01-01

    Acquisition of knowledge of the nature and DNA content of B chromosomes has been triggered by a collection of molecular techniques, one of which, microdissection, has provided interesting results in a number of B chromosome systems. Here we provide the first data on the molecular composition of B chromosomes in Locusta migratoria, after microdissection of the B and X chromosomes, DNA amplification by one (B) or two (X) different methods, and chromosome painting. The results showed that B chromosomes share at least two types of repetitive DNA sequences with the A chromosomes, suggesting that Bs in this species most likely arose intraspecifically. One of these repetitive DNAs is located on the heterochromatic distal half of the B chromosome and in the pericentromeric regions of about half of the A chromosomes, including the X. The other type of repetitive DNA is located interspersedly over the non-centromeric euchromatic regions of all A chromosomes and in an interstitial part of the proximal euchromatic half of the B chromosome. Chromosome painting, however, did not provide results sufficiently reliable to determine, in this species, which A chromosome gave rise to the B; this might be done by detailed analysis of the microdissected DNA sequences.

  1. A replication study of GWAS-derived lipid genes in Asian Indians: the chromosomal region 11q23.3 harbors loci contributing to triglycerides.

    Directory of Open Access Journals (Sweden)

    Timothy R Braun

    Full Text Available Recent genome-wide association scans (GWAS and meta-analysis studies on European populations have identified many genes previously implicated in lipid regulation. Validation of these loci on different global populations is important in determining their clinical relevance, particularly for development of novel drug targets for treating and preventing diabetic dyslipidemia and coronary artery disease (CAD. In an attempt to replicate GWAS findings on a non-European sample, we examined the role of six of these loci (CELSR2-PSRC1-SORT1 rs599839; CDKN2A-2B rs1333049; BUD13-ZNF259 rs964184; ZNF259 rs12286037; CETP rs3764261; APOE-C1-C4-C2 rs4420638 in our Asian Indian cohort from the Sikh Diabetes Study (SDS comprising 3,781 individuals (2,902 from Punjab and 879 from the US. Two of the six SNPs examined showed convincing replication in these populations of Asian Indian origin. Our study confirmed a strong association of CETP rs3764261 with high-density lipoprotein cholesterol (HDL-C (p = 2.03×10(-26. Our results also showed significant associations of two GWAS SNPs (rs964184 and rs12286037 from BUD13-ZNF259 near the APOA5-A4-C3-A1 genes with triglyceride (TG levels in this Asian Indian cohort (rs964184: p = 1.74×10(-17; rs12286037: p = 1.58×10(-2. We further explored 45 SNPs in a ∼195 kb region within the chromosomal region 11q23.3 (encompassing the BUD13-ZNF259, APOA5-A4-C3-A1, and SIK3 genes in 8,530 Asian Indians from the London Life Sciences Population (LOLIPOP (UK and SDS cohorts. Five more SNPs revealed significant associations with TG in both cohorts individually as well as in a joint meta-analysis. However, the strongest signal for TG remained with BUD13-ZNF259 (rs964184: p = 1.06×10(-39. Future targeted deep sequencing and functional studies should enhance our understanding of the clinical relevance of these genes in dyslipidemia and hypertriglyceridemia (HTG and, consequently, diabetes and CAD.

  2. [Differentiation of spa types and staphylococcal cassette chromosome mec (SCCmec) in clinical methicillin-resistant Staphylococcus aureus isolated in medical sites of Gdańsk region].

    Science.gov (United States)

    Kasprzyk, Joanna; Piechowicz, Lidia; Wiśniewska, Katarzyna; Dziewit, Łukasz; Bronk, Marek; Świeć, Krystyna

    2015-01-01

    Methicillin-resistant Staphylococcus aureus bacteria are one of the key etiological factors of hospital-acquired and community-acquired infections. MRSA strains have an ability of causing a broad spectrum infections: from a relatively mild skin infections to severe life-threatening systemic infections. They are characterized by multi-drug resistance, virulence of a number of factors, may clonally spread within the hospitals and between hospitals. The study embraced a number of 75 isolates of MRSA isolated from patients of 7 medical sites of the Gdansk region within the period of six months (June to December 2013). Strains have derived from various clinical materials, both of hospitalized patients (n=59) and outpatient (n=16). The isolates were tested for the susceptibility to antimicrobial agents accordance with the guidelines EUCAST. To estimate of the variability of occurrence of S. aureus clones used were standard spa gene, consisting in the amplified polymorphic region of the X gene encoding the protein A gene (spa). After receiving the results, a spa types were identified using international database Ridom Spa Server (www.spaserver.ridom.de). To determine the polymorphism cassette carrying the inecA gene from MRSA strains, used typing five major chromosomal cassette SCCmec (I-V) by multiplex PCR. MRSA population genetic analysis carried out on the basis of typing SCCmec cassettes and spa gene has showed a predominance of strains with SCCmec type II casette (46.7%) and SCCmec IV casette (38.7%). Less frequently detected were strains containing SCCmec I cassette (12.0%) and SCCmec III cassette (2.6%). Spa typing revealed the presence of 13 gene types in MRSA. The most frequently observed spa types were: t151 (24.0%), t003 (16.0%) in strains of the SCCmec II cassette and t437 (16.0%) and t008 (14.8%) in the isolates with SCCmec cassette IV, whereas staphylococcus with the type of spa t011 (12.0%) had SCCmec cassette I. In our population most frequent strains

  3. [Dicentric Y chromosome].

    Science.gov (United States)

    Abdelmoula, N Bouayed; Amouri, A

    2005-01-01

    Dicentric Y chromosomes are the most common Y structural abnormalities and their influence on gonadal and somatic development is extremely variable. Here, we report the third comprehensive review of the literature concerning dicentric Y chromosomes reported since 1994. We find 78 new cases for which molecular studies (PCR or FISH) have been widely applied to investigate SRY (68% of cases), GBY, ZFY, RFS4Y, GCY and different genes at AZF region. For dic(Yq), all cases (n = 20) were mosaic for 45,X and 4 of them were also mosaic for a 46,XY cell line. When breakpoints were available (15/20 cases), they were in Yp11. 50% of cases were phenotypic female and 20% phenotypic male while 20% of cases were reported with gonadal dysgenesis. Gonadal histology was defined in 8 cases but only in one case, gonadal tissu was genetically investigated because of gonadoblastoma. For dic(Yp) (n = 55), mosaicism concerned only 45,X cell line and was found in 50 cases while the remainder five cases were homogeneous. When breakpoints were available, it was at Yq11 in 50 cases and at Yq12 in two cases. 54% of cases were phenotypic female, 26% were phenotypic male and 18% were associated with genitalia ambiguous. SRY was analyzed in 33 cases, sequenced in 9 cases and was muted in only one case. Gonads were histologically explored in 34 cases and genetically investigated in 8 cases. Gonadoblastoma was found in only two cases. Through this review, it seems that phenotype-genotype correlations are still not possible and that homogeneous studies of dic(Y) in more patients using molecular tools for structural characterization of the rearranged Y chromosome and assessment of mosaicism in many organs are necessary to clarify the basis of the phenotypic heterogeneity of dicentric Y chromosomes and then to help phenotypic prediction of such chromosome rearrangement.

  4. Comparative analysis by chromosome painting of the sex chromosomes in arvicolid rodents.

    Science.gov (United States)

    Acosta, M J; Romero-Fernández, I; Sánchez, A; Marchal, J A

    2011-01-01

    Sex chromosome evolution in mammals has been extensively investigated through chromosome-painting analyses. In some rodent species from the subfamily Arvicolinae the sex chromosomes contain remarkable features such as giant size, a consequence of heterochromatic enlargement, or asynaptic behaviour during male meiosis. Here, we have made a comparative study of the sex chromosomes in 6 arvicolid species using different probes from the X and Y chromosomes of 3 species, in order to gain knowledge about intra- or interspecific preservation of euchromatic regions. Our results clearly reveal poor conservation of the euchromatic region of the Y chromosome within these species, while the euchromatin on the X chromosome is extremely well preserved. Furthermore, we detected no clear correlation between the synaptic/asynaptic behaviour of the sex chromosomes, and the presence or absence of sequence homology within their euchromatic regions. Notably, our study has shown a new relationship between the giant sex chromosomes of 2 species, Microtus agrestis and Microtus cabrerae, that is, both X and Y share a novel region of common sequences in the euchromatin that is not present in the other species analysed. This interspecific euchromatic conservation, limited to the giant sex chromosomes, could point towards a common evolutionary origin for the heterochromatic enlargement process that has characterized the evolution of the sex chromosomes in some arvicolid species.

  5. Healing of Broken Linear Dicentric Chromosomes in Yeast

    OpenAIRE

    Haber, James E; Thorburn, Patricia C.

    1984-01-01

    In yeast, meiotic recombination between a linear chromosome III and a haploid-viable circular chromosome will yield a dicentric, tandemly duplicated chromosome. Spores containing apparently intact dicentric chromosomes were recovered from tetrads with three viable spores. The spore containing the dicentric inherited URA3 (part of the recombinant DNA used to join regions near the ends of the chromosome into a circle) as well as HML, HMR and MAL2 (located near the two ends of a linear but dele...

  6. A gene-based high-resolution comparative radiation hybrid map as a framework for genome sequence assembly of a bovine chromosome 6 region associated with QTL for growth, body composition, and milk performance traits

    Directory of Open Access Journals (Sweden)

    Laurent Pascal

    2006-03-01

    Full Text Available Abstract Background A number of different quantitative trait loci (QTL for various phenotypic traits, including milk production, functional, and conformation traits in dairy cattle as well as growth and body composition traits in meat cattle, have been mapped consistently in the middle region of bovine chromosome 6 (BTA6. Dense genetic and physical maps and, ultimately, a fully annotated genome sequence as well as their mutual connections are required to efficiently identify genes and gene variants responsible for genetic variation of phenotypic traits. A comprehensive high-resolution gene-rich map linking densely spaced bovine markers and genes to the annotated human genome sequence is required as a framework to facilitate this approach for the region on BTA6 carrying the QTL. Results Therefore, we constructed a high-resolution radiation hybrid (RH map for the QTL containing chromosomal region of BTA6. This new RH map with a total of 234 loci including 115 genes and ESTs displays a substantial increase in loci density compared to existing physical BTA6 maps. Screening the available bovine genome sequence resources, a total of 73 loci could be assigned to sequence contigs, which were already identified as specific for BTA6. For 43 loci, corresponding sequence contigs, which were not yet placed on the bovine genome assembly, were identified. In addition, the improved potential of this high-resolution RH map for BTA6 with respect to comparative mapping was demonstrated. Mapping a large number of genes on BTA6 and cross-referencing them with map locations in corresponding syntenic multi-species chromosome segments (human, mouse, rat, dog, chicken achieved a refined accurate alignment of conserved segments and evolutionary breakpoints across the species included. Conclusion The gene-anchored high-resolution RH map (1 locus/300 kb for the targeted region of BTA6 presented here will provide a valuable platform to guide high-quality assembling and

  7. Chromosome 19 International Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Pericak-Vance, M.A. (Duke Univ., Durham, NC (United States). Medical Center); Ropers, H.H. (Univ. Hospital Nijmegen, (The Netherlands). Dept. of Human Genetics); Carrano, A.J. (Lawrence Livermore National Lab., CA (United States))

    1993-01-04

    The Second International Workshop on Human Chromosome 19 was hosted on January 25 and 26, 1992, by the Department of Human Genetics, University Hospital Nijmegen, The Netherlands, at the 'Meerdal Conference Center'. The workshop was supported by a grant from the European Community obtained through HUGO, the Dutch Research Organization (NWO) and the Muscular Dystrophy Association (MDA). Travel support for American participants was provided by the Department of Energy. The goals of this workshop were to produce genetic, physical and integrated maps of chromosome 19, to identify inconsistencies and gaps, and to discuss and exchange resources and techniques available for the completion of these maps. The second day of the meeting was largely devoted to region or disease specific efforts. In particular, the meeting served as a platform for assessing and discussing the recent progress made into the molecular elucidation of myotonic dystrophy.

  8. Mitotic chromosome condensation in vertebrates

    Energy Technology Data Exchange (ETDEWEB)

    Vagnarelli, Paola, E-mail: P.Vagnarelli@ed.ac.uk

    2012-07-15

    Work from several laboratories over the past 10-15 years has revealed that, within the interphase nucleus, chromosomes are organized into spatially distinct territories [T. Cremer, C. Cremer, Chromosome territories, nuclear architecture and gene regulation in mammalian cells, Nat. Rev. Genet. 2 (2001) 292-301 and T. Cremer, M. Cremer, S. Dietzel, S. Muller, I. Solovei, S. Fakan, Chromosome territories-a functional nuclear landscape, Curr. Opin. Cell Biol. 18 (2006) 307-316]. The overall compaction level and intranuclear location varies as a function of gene density for both entire chromosomes [J.A. Croft, J.M. Bridger, S. Boyle, P. Perry, P. Teague,W.A. Bickmore, Differences in the localization and morphology of chromosomes in the human nucleus, J. Cell Biol. 145 (1999) 1119-1131] and specific chromosomal regions [N.L. Mahy, P.E. Perry, S. Gilchrist, R.A. Baldock, W.A. Bickmore, Spatial organization of active and inactive genes and noncoding DNA within chromosome territories, J. Cell Biol. 157 (2002) 579-589] (Fig. 1A, A'). In prophase, when cyclin B activity reaches a high threshold, chromosome condensation occurs followed by Nuclear Envelope Breakdown (NEB) [1]. At this point vertebrate chromosomes appear as compact structures harboring an attachment point for the spindle microtubules physically recognizable as a primary constriction where the two sister chromatids are held together. The transition from an unshaped interphase chromosome to the highly structured mitotic chromosome (compare Figs. 1A and B) has fascinated researchers for several decades now; however a definite picture of how this process is achieved and regulated is not yet in our hands and it will require more investigation to comprehend the complete process. From a biochemical point of view a vertebrate mitotic chromosomes is composed of DNA, histone proteins (60%) and non-histone proteins (40%) [6]. I will discuss below what is known to date on the contribution of these two different classes

  9. Disgenesia gonadal mixta con fórmula cromosómica 45,X/46,X, (mar. Presentación de una paciente Mixed gonodal dysgenesis with chromosomic formula 45,X/46,X (mar. A case report

    Directory of Open Access Journals (Sweden)

    Pedro González Fernández

    2002-12-01

    Full Text Available Se presentó una paciente con estigmas turnerianos y cariotipo 45,X/46,XX con diagnóstico inicial de síndrome de Turner a la que se le realizó clitoridectomía por hipertrofia del clítoris a los 8 meses de edad. Se reevaluó a los 6 años de edad y se le realizó cariotipo con técnicas de bandas G (GTG con fórmula cromosómica de 45,X/46,X, (cromosoma marcador -mar; dicho marcador dio la impresión de una deleción del cromosoma X desde Xq13 ®Xq ter y Xp22 ®Xp ter. Se completó dicho estudio con técnica molecular de reacción en cadena de la polimerasa (PCR y se identificó el gen SRY en el cromosoma marcador. Se realizó intervención quirúrgica por mínimo acceso y se comprobó ausencia de útero así como trompa en el lado derecho con ausencia de gónada y en el lado opuesto, testículo rudimentario; se planteó el diagnóstico de disgenesia gonadal mixta.A patient with Turner stigmas and karyotype 45,X/46,XX with initial diagnosis of Turner's syndrome is presented. Clitoridectomy was performed due to hypertrophy of the clitoris when she was 8. She was reevaluated at 6 and karyotype was made by using G bands techniques (GTG with chromosomic formula of 45,X/46,X, (marker chromosome -mar; such marker gave the impression of a deletion of chromosome X from Xq13 ®Xq ter and Xp22 ®Xp ter. This study was completed with the molecular technique of polymerase chain reaction (PCR and the SRY gene was identified in the marker chromosome. The patient underwent minimum access surgery and it was proved the absence of uterus and tube on the right side with no gonad and a rudimentary testis on the opposite side. Mixed gonodal dysgenesis was diagnosed.

  10. Sex-determining region of Y-chromosome (Sry) : master switch of sex determination%Y染色体性别决定区(Sry):性别决定关键开关

    Institute of Scientific and Technical Information of China (English)

    裴开颜; 王介东

    2012-01-01

    性发育异常在人类遗传性疾病中很常见,因此性别决定在临床和生物学研究中非常重要.Y染色体性别决定区(sex-determining region of Y-chromosome,Sry)即哺乳动物Y染色体上的睾丸决定基因片段,与性别决定密切相关.本文对Sry基因的结构功能和表达调节及其相关的性别决定分子机制进行了综述.%Sex determination is very important in clinical and biological medicine because sex development disorders are the most common genetic diseases in humans. Sex-determining region of Y-chromosome (Sry) is the mammalian Y-chromosomal testis-determining gene. It is bound up with sex determination. In this paper, we consider issues related to Sry structure and function, its expression and regulation, and relevant molecular mechanisms of sex determination.

  11. Chromosomal Microarray Analysis in Fetuses with Growth Restriction and Normal Karyotype: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Borrell, Antoni; Grande, Maribel; Pauta, Montse; Rodriguez-Revenga, Laia; Figueras, Francesc

    2017-09-09

    To perform a systematic review of the literature and a meta-analysis to estimate the incremental yield of chromosomal microarray analysis (CMA) over karyotyping in fetal growth restriction (FGR). This was a systematic review conducted in accordance with the PRISMA criteria. All articles identified in PubMed, Ovid Medline, and ISI Web of Knowledge (Web of Science) from January 2009 to November 2016 describing pathogenic copy number variants (CNVs) in fetuses with growth restriction were included. Case reports were excluded. Risk differences were pooled to estimate the overall and stratified CMA incremental yield. Ten studies with full data available met the inclusion criteria for analysis. Combined data from these studies revealed a 4% (95% confidence interval [CI] 1-6%) incremental yield of CMA over karyotyping in nonmalformed growth-restricted fetuses, and a 10% (95% CI 6-14%) incremental yield in FGR when associated with fetal malformations. The most frequently found pathogenic CNVs were 22q11.2 duplication, Xp22.3 deletion, and 7q11.23 deletion (Williams-Beuren syndrome), particularly in isolated FGR. The use of genomic CMA provides a 4% incremental yield of detecting pathogenic CNVs in fetuses with isolated growth restriction and normal karyotype. © 2017 S. Karger AG, Basel.

  12. Chromosomal and regional localization of the loci for IGKC, IGGC, ALDB, HOXB, GPT, and PRNP in the American mink (Mustela vison): comparisons with human and mouse

    DEFF Research Database (Denmark)

    Khlebodarova, TM; Malchenko, Sergey; Matveeva, NM;

    1995-01-01

    Chromosomal localization of the genes for gamma- and kappa-immunoglobulins (IGGC and IGKC, respectively), aldolase B (ALDB), prion protein (PRNP), homeo box B (HOXB), and glutamate pyruvate transaminase (GPT) were determined with the use of mink-rodent hybrid cells. Analysis of segregation...

  13. Systematic characterisation of disease associated balanced chromosome rearrangements by FISH: cytogenetically and genetically anchored YACs identify microdeletions and candidate regions for mental retardation genes

    DEFF Research Database (Denmark)

    Wirth, J; Nothwang, H G; van der Maarel, S

    1999-01-01

    Disease associated balanced chromosome rearrangements (DBCRs) have been instrumental in the isolation of many disease genes. To facilitate the molecular cytogenetic characterisation of DBCRs, we have generated a set of >1200 non-chimeric, cytogenetically and genetically anchored CEPH YACs, on ave...

  14. Fine mapping of the chromosome 5B region carrying closely linked rust resistance genes Yr47 and Lr52 in wheat

    Science.gov (United States)

    The widely effective and linked rust resistance genes Yr47 and Lr52 were previously mapped in the short arm of chromosome 5B in two F3 populations (Aus28183/Aus27229 and Aus28187/Aus27229). The Aus28183/Aus27229 F3 population was advanced to generate an F6 recombinant inbred line (RIL) population t...

  15. Detailed phenotype-genotype study in five patients with chromosome 6q16 deletion : narrowing the critical region for Prader-Willi-like phenotype

    NARCIS (Netherlands)

    Bonaglia, Maria Clara; Ciccone, Roberto; Gimelli, Giorgio; Gimelli, Stefania; Marelli, Susan; Verheij, Joke; Giorda, Roberto; Grasso, Rita; Borgatti, Renato; Pagone, Filomena; Rodriguez, Laura; Martinez-Frias, Maria-Luisa; van Ravenswaaij, Conny; Zuffardi, Orsetta

    2008-01-01

    Most patients with an interstitial deletion of 6q16 have Prader-Willi-like phenotype, featuring obesity, hypotonia, short hands and feet, and developmental delay. In all reported studies, the chromosome rearrangement was detected by karyotype analysis, which provides an overview of the entire genome

  16. Extension, single-locus conversion and physical mapping of sex chromosome sequences identify the Z microchromosome and pseudo-autosomal region in a dragon lizard, Pogona vitticeps.

    Science.gov (United States)

    Quinn, A E; Ezaz, T; Sarre, S D; Graves, Ja Marshall; Georges, A

    2010-04-01

    Distribution of temperature-dependent sex determination (TSD) and genotypic sex determination (GSD) across the phylogeny of dragon lizards implies multiple independent origins of at least one, and probably both, modes of sex determination. Female Pogona vitticeps are the heterogametic sex, but ZZ individuals reverse to a female phenotype at high incubation temperatures. We used reiterated genome walking to extend Z and W chromosome-linked amplified fragment length polymorphism (AFLP) markers, and fluorescence in situ hybridization for physical mapping. One extended fragment hybridized to both W and Z microchromosomes, identifying the Z microchromosome for the first time, and a second hybridized to the centromere of all microchromosomes. W-linked sequences were converted to a single-locus PCR sexing assay. P. vitticeps sex chromosome sequences also shared homology with several other Australian dragons. Further physical mapping and isolation of sex-specific bacterial artificial chromosome clones will provide insight into the evolution of sex determination and sex chromosomes in GSD and TSD dragon lizards.

  17. Homologies between human and marmoset (Callithrix jacchus) chromosomes revealed by comparative chromosome painting

    Energy Technology Data Exchange (ETDEWEB)

    Sherlock, J.K.; Griffin, D.K.; Delhanty, J.D.A.; Parrington, J.M. [Univ. College London (United Kingdom)

    1996-04-15

    Regions of DNA homology between human and marmoset (Callithrix jacchus) chromosomes have been demonstrated using fluorescence in situ hybridization. All 24 chromosome paints and two centromere repeat sequences from Homo sapiens (HSA) have been annealed to previously G-banded metaphase spreads of Callithrix jacchus. All human paint probes, except Y, successfully hybridized to marmoset chromosomes. Fifteen of them hybridized to one region only, seven to two regions, and paint 1 to three regions. Homologies proposed from previous banding comparisons have been confirmed for HSA 2, 4-6, 10-12, 18, 19, 21, and X and partially confirmed for HSA 1 and 3, but were not in agreement for HSA 14 and 17. Human centromere repeat sequences for X and 18 did not hybridize to marmoset chromosomes. Because, at present, there is the confusing situation of several different numbering systems for marmoset chromosomes, we propose a new simpler nomenclature based on descending order of chromosome size. 25 refs., 3 figs.

  18. Garcia chromosomal aneusomy + cytology — EDRN Public Portal

    Science.gov (United States)

    Fluorescence in situ hybridization (FISH) assay is used to monitor levels of chromosome copies in interphase cells. Multicolor FISH proes simultaneously target four different chromosome regions in a single cell.

  19. Sex-specific effects on spatial learning and memory, and sex-independent effects on blood pressure of a <3.3 Mbp rat chromosome 2 QTL region in Dahl salt-sensitive rats.

    Directory of Open Access Journals (Sweden)

    Victoria L Herrera

    Full Text Available Epidemiological studies have consistently found that hypertension is associated with poor cognitive performance. We hypothesize that a putative causal mechanism underlying this association is due to genetic loci affecting both blood pressure and cognition. Consistent with this notion, we reported several blood pressure (BP quantitative trait loci (QTLs that co-localized with navigational performance (Nav-QTLs influencing spatial learning and memory in Dahl rats. The present study investigates a chromosome 2 region harboring BP-f4 and Nav-8 QTLs. We developed two congenic strains, S.R2A and S.R2B introgressing Dahl R-chromosome 2 segments into Dahl S chromosome 2 region spanning BP-f4 and Nav-8 QTLs. Radiotelemetric blood pressure analysis identified only S.R2A congenic rats with lower systolic blood pressure (females: -26.0 mmHg, P = 0.003; males: -30.9 mmHg, P<1×10(-5, diastolic blood pressure (females: -21.2 mmHg, P = 0.01; males: -25.7 mmHg, P<1×10(-5, and mean arterial pressure (females: -23.9 mmHg, P = 0.004; males: -28.0 mmHg, P<1×10(-5 compared with corresponding Dahl S controls, confirming the presence of BP-f4 QTL on rat chromosome 2. The S.R2B congenic segment did not affect blood pressure. Testing of S.R2A, S.R2B, and Dahl S male rats in the Morris water maze (MWM task revealed significantly decreased spatial navigation performance in S.R2A male congenic rats when compared with Dahl S male controls (P<0.05. The S.R2B congenic segment did not affect performance of the MWM task in males. The S.R2A female rats did not differ in spatial navigation when compared with Dahl S female controls, indicating that the Nav-8 effect on spatial navigation is male-specific. Our results suggest the existence of a single QTL on chromosome 2 176.6-179.9 Mbp region which affects blood pressure in both males and females and cognition solely in males.

  20. Sequencing papaya X and Yh chromosomes reveals molecular basis of incipient sex chromosome evolution.

    Science.gov (United States)

    Wang, Jianping; Na, Jong-Kuk; Yu, Qingyi; Gschwend, Andrea R; Han, Jennifer; Zeng, Fanchang; Aryal, Rishi; VanBuren, Robert; Murray, Jan E; Zhang, Wenli; Navajas-Pérez, Rafael; Feltus, F Alex; Lemke, Cornelia; Tong, Eric J; Chen, Cuixia; Wai, Ching Man; Singh, Ratnesh; Wang, Ming-Li; Min, Xiang Jia; Alam, Maqsudul; Charlesworth, Deborah; Moore, Paul H; Jiang, Jiming; Paterson, Andrew H; Ming, Ray

    2012-08-21

    Sex determination in papaya is controlled by a recently evolved XY chromosome pair, with two slightly different Y chromosomes controlling the development of males (Y) and hermaphrodites (Y(h)). To study the events of early sex chromosome evolution, we sequenced the hermaphrodite-specific region of the Y(h) chromosome (HSY) and its X counterpart, yielding an 8.1-megabase (Mb) HSY pseudomolecule, and a 3.5-Mb sequence for the corresponding X region. The HSY is larger than the X region, mostly due to retrotransposon insertions. The papaya HSY differs from the X region by two large-scale inversions, the first of which likely caused the recombination suppression between the X and Y(h) chromosomes, followed by numerous additional chromosomal rearrangements. Altogether, including the X and/or HSY regions, 124 transcription units were annotated, including 50 functional pairs present in both the X and HSY. Ten HSY genes had functional homologs elsewhere in the papaya autosomal regions, suggesting movement of genes onto the HSY, whereas the X region had none. Sequence divergence between 70 transcripts shared by the X and HSY revealed two evolutionary strata in the X chromosome, corresponding to the two inversions on the HSY, the older of which evolved about 7.0 million years ago. Gene content differences between the HSY and X are greatest in the older stratum, whereas the gene content and order of the collinear regions are identical. Our findings support theoretical models of early sex chromosome evolution.

  1. Physical mapping studies at D15S10: Implications for candidate gene identification in the Angelman syndrome/Prader-Willi syndrome chromosome region of 15q11-q13

    Energy Technology Data Exchange (ETDEWEB)

    Woodage, T.; Lindeman, R.; Deng, Z.M.; Fimmel, A.; Trent, R.J. (Royal Prince Alfred Hospital, New South Wales (Australia)); Smith, A. (Children' s Hospital, New South Wales (Australia))

    1994-01-01

    The Angelman syndrome (AS) and Prader-Willi syndrome (PWS) loci have been mapped to chromosome 15q11-q13. Chromosomal deletions of differing parental origin in the two syndromes have been interpreted as being due to genetic imprinting. Molecular analysis of patients with varying deletions has localized the AS locus to the interval between D15S113 and GABRB3 and the PWS locus between D15S13 and D15S113. In the present study, DNA cloning and physical mapping techniques have been used to characterize the AS/PWS chromosome region in the vicinity of D15S10, a locus that is telomeric to D15S113 and centromeric to GABRB3. A CpG island near TD3-21 at D15S10 has been cloned, allowing the identification of a widely expressed 4.5-kb transcript and providing a novel DNA marker, OP3, at this locus. OP3 and TD3-21 have been used to construct a long-range physical map extending over approximately 2800 kb. Clusters of rare-cutting restriction sites on this map locate four other CpG islands. Since these CpG islands lie within the minimum deletion intervals for AS and PWS, they mark the possible locations of candidate genes for the two syndromes. 13 refs., 2 figs.

  2. Unusual maternal uniparental isodisomic x chromosome mosaicism with asymmetric y chromosomal rearrangement.

    Science.gov (United States)

    Lee, B Y; Kim, S Y; Park, J Y; Choi, E Y; Kim, D J; Kim, J W; Ryu, H M; Cho, Y H; Park, S Y; Seo, J T

    2014-01-01

    Infertile men with azoospermia commonly have associated microdeletions in the azoospermia factor (AZF) region of the Y chromosome, sex chromosome mosaicism, or sex chromosome rearrangements. In this study, we describe an unusual 46,XX and 45,X mosaicism with a rare Y chromosome rearrangement in a phenotypically normal male patient. The patient's karyotype was 46,XX[50]/45,X[25]/46,X,der(Y)(pter→q11.222::p11.2→pter)[25]. The derivative Y chromosome had a deletion at Yq11.222 and was duplicated at Yp11.2. Two copies of the SRY gene were confirmed by fluorescence in situ hybridization analysis, and complete deletion of the AZFb and AZFc regions was shown by multiplex-PCR for microdeletion analysis. Both X chromosomes of the predominant mosaic cell line (46,XX) were isodisomic and derived from the maternal gamete, as determined by examination of short tandem repeat markers. We postulate that the derivative Y chromosome might have been generated during paternal meiosis or early embryogenesis. Also, we suggest that the very rare mosaicism of isodisomic X chromosomes might be formed during maternal meiosis II or during postzygotic division derived from the 46,X,der(Y)/ 45,X lineage because of the instability of the derivative Y chromosome. To our knowledge, this is the first confirmatory study to verify the origin of a sex chromosome mosaicism with a Y chromosome rearrangement.

  3. Sequence and functional analysis of GLUT10: a glucose transporter in the Type 2 diabetes-linked region of chromosome 20q12-13.1.

    Science.gov (United States)

    Dawson, P A; Mychaleckyj, J C; Fossey, S C; Mihic, S J; Craddock, A L; Bowden, D W

    2001-01-01

    We have carried out a detailed sequence and functional analysis of a novel human facilitative glucose transporter, designated GLUT10, located in the Type 2 diabetes-linked region of human chromosome 20q12-13.1. The GLUT10 gene is located between D20S888 and D20S891 and is encoded by 5 exons spanning 26.8 kb of genomic DNA. The human GLUT10 cDNA encodes a 541 amino acid protein that shares between 31 and 35% amino acid identity with human GLUT1-8. The predicted amino acid sequence of GLUT10 is nearly identical in length to the recently described GLUT9 homologue, but is longer than other known members of the GLUT family. In addition, we have cloned the mouse cDNA homolog of GLUT10 that encodes a 537 amino acid protein that shares 77.3% identity with human GLUT10. The amino acid sequence probably has 12 predicted transmembrane domains and shares characteristics of other mammalian glucose transporters. Human and mouse GLUT10 retain several sequence motifs characteristic of mammalian glucose transporters including VP497ETKG in the cytoplasmic C-terminus, G73R[K,R] between TMD2 and TMD3 (PROSITE PS00216), VD92RAGRR between TMD8 and TMD9 (PROSITE PS00216), Q242QLTG in TMD7, and tryptophan residues W430 (TMD10) and W454 (TMD11), that correspond to trytophan residues previously implicated in GLUT1 cytochalasin B binding and hexose transport. Neither human nor mouse GLUT10 retains the full P[E,D,N]SPR motif after Loop6 but instead is replaced with P186AG[T,A]. A PROSITE search also shows that GLUT10 has lost the SUGAR TRANSPORT 2 pattern (PS00217), a result of the substitution G113S in TMD4, while all other known human GLUTs retain the glycine and the pattern match. The significance of this substitution is unknown. Sites for N-linked glycosylation are predicted at N334ATG between TMD8 and TMD9 and N526STG in the cytoplasmic C-terminus. Northern hybridization analysis identified a single 4.4-kb transcript for GLUT10 in human heart, lung, brain, liver, skeletal muscle

  4. CHROMOSOME ABNORMALITIES IN INFERTILITY

    Directory of Open Access Journals (Sweden)

    Mateja Smogavec

    2009-08-01

    Conclusions Chromosomal analysis is an important method in diagnostic procedures of infertility, because chromosomal abnormalities could play the important role in etiology of infertility and are more frequently detected in this group of patients compared to general population. In the infertile couples balanced chromosomal abnormalities are the main cause of spontaneous abortions. Sex chromosome aneuploidies are highly correlated to infertility of females and males.

  5. The human intrinsic factor-vitamin B12 receptor, cubilin: molecular characterization and chromosomal mapping of the gene to 10p within the autosomal recessive megaloblastic anemia (MGA1) region

    DEFF Research Database (Denmark)

    Kozyraki, R; Kristiansen, M; Silahtaroglu, A

    1998-01-01

    -5445 on the short arm of chromosome 10. This is within the autosomal recessive megaloblastic anemia (MGA1) 6-cM region harboring the unknown recessive-gene locus of juvenile megaloblastic anemia caused by intestinal malabsorption of cobalamin (Imerslund-Gräsbeck's disease). In conclusion, the present...... molecular and genetic information on human cubilin now provides circumstantial evidence that an impaired synthesis, processing, or ligand binding of cubilin is the molecular background of this hereditary form of megaloblastic anemia. Udgivelsesdato: 1998-May-15...

  6. 3D/4D architecture of chromosomal break point regions in the cell nucleus following irradiation of normal cells and tumor cells; 3D/4D Architektur von chromosomalen Bruchpunktregionen im Zellkern nach Bestrahlung von Normalzellen und Tumorzellen

    Energy Technology Data Exchange (ETDEWEB)

    Hausmann, M.; Cremer, C.; Friedl, A.; Dollinger, G.; Loebrich, M.; Friedland, W.

    2015-01-15

    The development of an effective analytical methodology for a correct description of oncogenic chromosomal aberrations is the challenge of medical radiobiology with respect to preventive therapeutic methods. Scope of the project was a better understanding of the behavior of break point regions dependent on the genome loci, the chromatin folding, the involved repair proteins and the beam quality with respect to an improvement and an efficient prognosis of the health consequences following radiation exposure. New microscopic insights in the normal cell nucleus are supposed to allow a better understanding of the spatial interactions on a molecular scale.

  7. Auditory function in the Tc1 mouse model of down syndrome suggests a limited region of human chromosome 21 involved in otitis media.

    Directory of Open Access Journals (Sweden)

    Stephanie Kuhn

    Full Text Available Down syndrome is one of the most common congenital disorders leading to a wide range of health problems in humans, including frequent otitis media. The Tc1 mouse carries a significant part of human chromosome 21 (Hsa21 in addition to the full set of mouse chromosomes and shares many phenotypes observed in humans affected by Down syndrome with trisomy of chromosome 21. However, it is unknown whether Tc1 mice exhibit a hearing phenotype and might thus represent a good model for understanding the hearing loss that is common in Down syndrome. In this study we carried out a structural and functional assessment of hearing in Tc1 mice. Auditory brainstem response (ABR measurements in Tc1 mice showed normal thresholds compared to littermate controls and ABR waveform latencies and amplitudes were equivalent to controls. The gross anatomy of the middle and inner ears was also similar between Tc1 and control mice. The physiological properties of cochlear sensory receptors (inner and outer hair cells: IHCs and OHCs were investigated using single-cell patch clamp recordings from the acutely dissected cochleae. Adult Tc1 IHCs exhibited normal resting membrane potentials and expressed all K(+ currents characteristic of control hair cells. However, the size of the large conductance (BK Ca(2+ activated K(+ current (I(K,f, which enables rapid voltage responses essential for accurate sound encoding, was increased in Tc1 IHCs. All physiological properties investigated in OHCs were indistinguishable between the two genotypes. The normal functional hearing and the gross structural anatomy of the middle and inner ears in the Tc1 mouse contrast to that observed in the Ts65Dn model of Down syndrome which shows otitis media. Genes that are trisomic in Ts65Dn but disomic in Tc1 may predispose to otitis media when an additional copy is active.

  8. Chromosomal painting and ZW sex chromosomes differentiation in Characidium (Characiformes, Crenuchidae

    Directory of Open Access Journals (Sweden)

    Artoni Roberto F

    2011-07-01

    Full Text Available Abstract Background The Characidium (a Neotropical fish group have a conserved diploid number (2n = 50, but show remarkable differences among species and populations in relation to sex chromosome systems and location of nucleolus organizer regions (NOR. In this study, we isolated a W-specific probe for the Characidium and characterized six Characidium species/populations using cytogenetic procedures. We analyzed the origin and differentiation of sex and NOR-bearing chromosomes by chromosome painting in populations of Characidium to reveal their evolution, phylogeny, and biogeography. Results A W-specific probe for efficient chromosome painting was isolated by microdissection and degenerate oligonucleotide primed-polymerase chain reaction (DOP-PCR amplification of W chromosomes from C. gomesi. The W probe generated weak signals dispersed on the proto sex chromosomes in C. zebra, dispersed signals in both W and Z chromosomes in C. lauroi and, in C. gomesi populations revealed a proximal site on the long arms of the Z chromosome and the entire W chromosome. All populations showed small terminal W probe sites in some autosomes. The 18S rDNA revealed distinctive patterns for each analyzed species/population with regard to proto sex chromosome, sex chromosome pair, and autosome location. Conclusions The results from dual-color fluorescence in situ hybridization (dual-color FISH using W and 18S rDNA probes allowed us to infer the putative evolutionary pathways for the differentiation of sex chromosomes and NORs, from structural rearrangements in a sex proto-chromosome, followed by gene erosion and heterochromatin amplification, morphological differentiation of the sex chromosomal pair, and NOR transposition, giving rise to the distinctive patterns observed among species/populations of Characidium. Biogeographic isolation and differentiation of sex chromosomes seem to have played a major role in the speciation process in this group of fish.

  9. Undetected sex chromosome aneuploidy by chromosomal microarray.

    Science.gov (United States)

    Markus-Bustani, Keren; Yaron, Yuval; Goldstein, Myriam; Orr-Urtreger, Avi; Ben-Shachar, Shay

    2012-11-01

    We report on a case of a female fetus found to be mosaic for Turner syndrome (45,X) and trisomy X (47,XXX). Chromosomal microarray analysis (CMA) failed to detect the aneuploidy because of a normal average dosage of the X chromosome. This case represents an unusual instance in which CMA may not detect chromosomal aberrations. Such a possibility should be taken into consideration in similar cases where CMA is used in a clinical setting.

  10. Schizophrenia and chromosomal deletions

    Energy Technology Data Exchange (ETDEWEB)

    Lindsay, E.A.; Baldini, A. [Baylor College of Medicine, Houston, TX (United States); Morris, M. A. [Univ. of Geneva School of Medicine, NY (United States)] [and others

    1995-06-01

    Recent genetic linkage analysis studies have suggested the presence of a schizophrenia locus on the chromosomal region 22q11-q13. Schizophrenia has also been frequently observed in patients affected with velo-cardio-facial syndrome (VCFS), a disorder frequently associated with deletions within 22q11.1. It has been hypothesized that psychosis in VCFS may be due to deletion of the catechol-o-methyl transferase gene. Prompted by these observations, we screened for 22q11 deletions in a population of 100 schizophrenics selected from the Maryland Epidemiological Sample. Our results show that there are schizophrenic patients carrying a deletion of 22q11.1 and a mild VCFS phenotype that might remain unrecognized. These findings should encourage a search for a schizophrenia-susceptibility gene within the deleted region and alert those in clinical practice to the possible presence of a mild VCFS phenotype associated with schizophrenia. 9 refs.

  11. Genetic screening for chromosomal abnormalities and Y chromosome microdeletions in Chinese infertile men.

    Science.gov (United States)

    Fu, Li; Xiong, Da-Ke; Ding, Xian-Ping; Li, Chuang; Zhang, Li-Yuan; Ding, Min; Nie, Shuang-Shuang; Quan, Qiang

    2012-06-01

    To investigate the frequency and type of both chromosomal abnormalities and Y chromosome microdeletions and analyze their association with defective spermatogenesis in Chinese infertile men. This is a single center study. Karyotyping using G-banding and screening for Y chromosome microdeletion by multiplex polymerase chain reaction(PCR)were performed in 200 controls and 1,333 infertile men, including 945 patients with non-obstructive azoospermia and 388 patients with severe oligozoospermia. Out of 1,333 infertile patients, 154(11.55%) presented chromosomal abnormalities. Of these, 139 of 945 (14.71%) were from the azoospermic and 15 of 388 (3.87%) from the severe oligozoospermic patient groups. The incidence of sex chromosomal abnormalities in men with azoospermia was 11.53% compared with 1.03% in men with severe oligozoospermia (P chromosome microdeletions. The incidence of azoospermia factor(AZF) microdeletion was 11.75% and 8.51% in patients with azoospermia and severe oligozoospermia respectively. Deletion of AZFc was the most common and deletions in AZFa or AZFab or AZFabc were found in azoospermic men. In addition, 34 patients had chromosomal abnormalities among the 144 patients with Y chromosome microdeletions. No chromosomal abnormality and microdeletion in AZF region were detected in controls. There was a high incidence (19.80%) of chromosomal abnormalities and Y chromosomal microdeletions in Chinese infertile males with azoospermia or severe oligozoospermia. These findings strongly suggest that genetic screening should be advised to infertile men before starting assisted reproductive treatments.

  12. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS.

    Science.gov (United States)

    DeJesus-Hernandez, Mariely; Mackenzie, Ian R; Boeve, Bradley F; Boxer, Adam L; Baker, Matt; Rutherford, Nicola J; Nicholson, Alexandra M; Finch, NiCole A; Flynn, Heather; Adamson, Jennifer; Kouri, Naomi; Wojtas, Aleksandra; Sengdy, Pheth; Hsiung, Ging-Yuek R; Karydas, Anna; Seeley, William W; Josephs, Keith A; Coppola, Giovanni; Geschwind, Daniel H; Wszolek, Zbigniew K; Feldman, Howard; Knopman, David S; Petersen, Ronald C; Miller, Bruce L; Dickson, Dennis W; Boylan, Kevin B; Graff-Radford, Neill R; Rademakers, Rosa

    2011-10-20

    Several families have been reported with autosomal-dominant frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), genetically linked to chromosome 9p21. Here, we report an expansion of a noncoding GGGGCC hexanucleotide repeat in the gene C9ORF72 that is strongly associated with disease in a large FTD/ALS kindred, previously reported to be conclusively linked to chromosome 9p. This same repeat expansion was identified in the majority of our families with a combined FTD/ALS phenotype and TDP-43-based pathology. Analysis of extended clinical series found the C9ORF72 repeat expansion to be the most common genetic abnormality in both familial FTD (11.7%) and familial ALS (23.5%). The repeat expansion leads to the loss of one alternatively spliced C9ORF72 transcript and to formation of nuclear RNA foci, suggesting multiple disease mechanisms. Our findings indicate that repeat expansion in C9ORF72 is a major cause of both FTD and ALS.

  13. Definition of the locus responsible for systemic carnitine deficiency within a 1.6-cM region of mouse chromosome 11 by detailed linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Okita, Kohei; Tokino, Takashi; Nishimori, Hiroyuki [Univ. of Tokyo (Japan)] [and others

    1996-04-15

    Carnitine is an essential cofactor for oxidation of mitochondrial fatty acids. Carnitine deficiency results in failure of energy production by mitochondria and leads to metabolic encephalopathy, lipid-storage myopathy, and cardiomyopathy. The juvenile visceral steatosis (JVS) mouse, an animal model of systemic carnitine deficiency, inherits the JVS phenotype in autosomal recessive fashion, through a mutant allele mapped to mouse chromosome 11. As a step toward identifying the gene responsible for JVS by positional cloning, we attempted to refine the jvs locus in the mouse by detailed linkage analysis with 13 microsatellite markers, using 190 backcross progeny. Among the 13 loci tested, 5 (defined by markers D11Mit24, D11Mit111,D11Nds9, D11Mit86, and D11Mit23) showed no recombination, with a maximum lod score of 52.38. Our results implied that the jvs gene can be sought on mouse chromosome 11 within a genetic distance no greater than about 1.6 cM. 21 refs., 2 figs.

  14. Mapping of the serotonin 5-HT{sub 1D{alpha}} autoreceptor gene (HTR1D) on chromosome 1 using a silent polymorphism in the coding region

    Energy Technology Data Exchange (ETDEWEB)

    Ozaki, N.; Lappalainen, J.; Linnoila, M. [National Institute on Alcohol Abuse and Alcoholism, Rockville, MD (United States)] [and others

    1995-04-24

    Serotonin (5-HT){sub ID} receptors are 5-HT release-regulating autoreceptors in the human brain. Abnormalities in brain 5-HT function have been hypothesized in the pathophysiology of various psychiatric disorders, including obsessive-compulsive disorder, autism, mood disorders, eating disorders, impulsive violent behavior, and alcoholism. Thus, mutations occurring in 5-HT autoreceptors may cause or increase the vulnerability to any of these conditions. 5-HT{sub 1D{alpha}} and 5-HT{sub 1D{Beta}} subtypes have been previously localized to chromosomes 1p36.3-p34.3 and 6q13, respectively, using rodent-human hybrids and in situ localization. In this communication, we report the detection of a 5-HT{sub 1D{alpha}} receptor gene polymorphism by single strand conformation polymorphism (SSCP) analysis of the coding sequence. The polymorphism was used for fine scale linkage mapping of 5-HT{sub 1D{alpha}} on chromosome 1. This polymorphism should also be useful for linkage studies in populations and in families. Our analysis also demonstrates that functionally significant coding sequence variants of the 5-HT{sub 1D{alpha}} are probably not abundant either among alcoholics or in the general population. 14 refs., 1 fig., 1 tab.

  15. Chromosome 5 and Parkinson disease.

    Science.gov (United States)

    Foroud, Tatiana; Pankratz, Nathan; Martinez, Maria

    2006-10-01

    Parkinson disease (PD) is the second most common neurodegenerative disorder. Despite the identification of five causative genes, the majority of PD etiology is still unknown. A region on chromosome 5q is one of the few regions of the genome found linked in multiple studies of familial PD. Analyses were performed using genotypic data from two independent research studies to evaluate rigorously the evidence of linkage on chromosome 5. The combined sample consisting of 1238 affected individuals from 569 multiplex PD families were genotyped for a common set of 20 microsatellite markers spanning an 80 cM region on chromosome 5q. Two disease models were employed and model-free linkage analyses were performed to detect linkage to a PD susceptibility gene and also to detect linkage to a quantitative phenotype, age of onset of PD. There was little evidence of linkage using either a narrower or broader disease definition (lod <0.5). Analyses employing age of onset of PD as the phenotype produced a lod score of 1.8. These results in a very large sample of familial PD suggest that it is unlikely that a PD susceptibility gene is located on chromosome 5q. Evidence for a locus contributing to the age of onset of PD is modest at best (empirical P-value=0.07).

  16. Characterization of X chromosome inactivation using integrated analysis of whole-exome and mRNA sequencing.

    Directory of Open Access Journals (Sweden)

    Szabolcs Szelinger

    Full Text Available In females, X chromosome inactivation (XCI is an epigenetic, gene dosage compensatory mechanism by inactivation of one copy of X in cells. Random XCI of one of the parental chromosomes results in an approximately equal proportion of cells expressing alleles from either the maternally or paternally inherited active X, and is defined by the XCI ratio. Skewed XCI ratio is suggestive of non-random inactivation, which can play an important role in X-linked genetic conditions. Current methods rely on indirect, semi-quantitative DNA methylation-based assay to estimate XCI ratio. Here we report a direct approach to estimate XCI ratio by integrated, family-trio based whole-exome and mRNA sequencing using phase-by-transmission of alleles coupled with allele-specific expression analysis. We applied this method to in silico data and to a clinical patient with mild cognitive impairment but no clear diagnosis or understanding molecular mechanism underlying the phenotype. Simulation showed that phased and unphased heterozygous allele expression can be used to estimate XCI ratio. Segregation analysis of the patient's exome uncovered a de novo, interstitial, 1.7 Mb deletion on Xp22.31 that originated on the paternally inherited X and previously been associated with heterogeneous, neurological phenotype. Phased, allelic expression data suggested an 83∶20 moderately skewed XCI that favored the expression of the maternally inherited, cytogenetically normal X and suggested that the deleterious affect of the de novo event on the paternal copy may be offset by skewed XCI that favors expression of the wild-type X. This study shows the utility of integrated sequencing approach in XCI ratio estimation.

  17. Genetic analysis of 17 Y-chromosomal STR loci of Chinese Tujia ethnic group residing in Youyang Region of Southern China.

    Science.gov (United States)

    Yang, Ya-Ran; Jing, Yu-Ting; Zhang, Guo-Dong; Fang, Xiang-Dong; Yan, Jiang-Wei

    2014-05-01

    Y-STR haplotype data were obtained in a population sample of 197 unrelated healthy male individuals of Chinese Tujia ethnic minority group residing in an autonomous county of Southern China using 17 Y-chromosome STR markers. A total of 197 haplotypes were identified in the set of Y-STR loci. The overall haplotype diversity for the Tujia population at 17 Y-STR loci was 1.0000±0.0005. Genetic distance was estimated between this population and other 14 Chinese populations including Paiwan and Atayal populations of Taiwan, and Southern Han, Dong, Jing, Miao, Yao, Zhuang, Yi, Maonan, She, Hui, Sala, and Tibetan ethnic groups. The results demonstrated that the 17 Y-STR loci analyzed were highly polymorphic in Tujia ethnic group examined and hence useful for forensic cases, paternity testing, and population genetic studies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Chromosomal Distribution of the 18S-5.8S-26S rDNA Loci and Heterogeneity of Nuclear ITS Regions in Thinopyrum intermedium (Poaceae: Triticeae)

    Institute of Scientific and Technical Information of China (English)

    LIDa-Yong; RUYan-Yan; ZHANGXue-Yong

    2004-01-01

    Fluorescent in situ hybridization (FISH) was used to investigate the chromosomal location of 18S-5.8S-26S rDNA loci in Thinopyrum intermedium (Host) Barkworth et Dewey (2n=6x=42). In all accessions and individuals studied, 3 or 4 pairs of major loci were detected. Subsequent genomic in situhybddization (GISH) analyses revealed that one pair was located on the ends of the short arms of one pair of homologous chromosomes of the St genome, while the other 2 or 3 pairs of major loci were located in the E genomes (including the Eo and Eb). It is suggested that 2 to 3 pairs of major loci were probably lost during the evolution of this hexaploid species. The variation in rDNA positions and copy numbers between the diploid donors and Th. interrnedium, as well as the diversity among the accessions of Th. intermedium confirmed that the rDNA gene family conveyed the characters of DNA mobile elements. The internal transcribed spacer (ITS) regions of the rDNA in Th. intermedium were also investigated. Sequence data of seven positive clones from one individual suggested high degree of individual heterogeneity exists among ITS repeats. Phylogenetic analyses showed that there were two distinct types of ITS sequences in Th. intermedium, one with homology to that of Pseudoroegneria species (St genome) and the other to that of the E genome diploid species. This showed that the ITS paralogues in Th. intermedium have not been uniformly homogenized by concerted evolution. The limitation of using the chromosomal location of rDNA loci for phylogenetic analysis is discussed.

  19. Chromosome Disorder Outreach

    Science.gov (United States)

    ... BLOG Join Us Donate You are not alone. Chromosome Disorder Outreach, Inc. is a non-profit organization, ... Support For all those diagnosed with any rare chromosome disorder. Since 1992, CDO has supported the parents ...

  20. Chromosome painting in plants.

    NARCIS (Netherlands)

    Schubert, I.; Fransz, P.F.; Fuchs, J.; Jong, de J.H.

    2001-01-01

    The current 'state-of-art' as to chromosome painting in plants is reviewed. We define different situations described as painting so far: i) Genomic in situ hybridisation (GISH) with total genomic DNA to distinguish alien chromosomes on the basis of divergent dispersed repeats, ii) 'Chromosomal in si

  1. ZEBRAFISH CHROMOSOME-BANDING

    NARCIS (Netherlands)

    PIJNACKER, LP; FERWERDA, MA

    1995-01-01

    Banding techniques were carried out on metaphase chromosomes of zebrafish (Danio rerio) embryos. The karyotypes with the longest chromosomes consist of 12 metacentrics, 26 submetacentrics, and 12 subtelocentrics (2n = 50). All centromeres are C-band positive. Eight chromosomes have a pericentric C-b

  2. Chromosome painting in plants.

    NARCIS (Netherlands)

    Schubert, I.; Fransz, P.F.; Fuchs, J.; Jong, de J.H.

    2001-01-01

    The current 'state-of-art' as to chromosome painting in plants is reviewed. We define different situations described as painting so far: i) Genomic in situ hybridisation (GISH) with total genomic DNA to distinguish alien chromosomes on the basis of divergent dispersed repeats, ii) 'Chromosomal in

  3. Chromosome I duplications in Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    McKim, K.S.; Rose, A.M. (Univ. of British Columbia, Vancouver (Canada))

    1990-01-01

    We have isolated and characterized 76 duplications of chromosome I in the genome of Caenorhabditis elegans. The region studied is the 20 map unit left half of the chromosome. Sixty-two duplications were induced with gamma radiation and 14 arose spontaneously. The latter class was apparently the result of spontaneous breaks within the parental duplication. The majority of duplications behave as if they are free. Three duplications are attached to identifiable sequences from other chromosomes. The duplication breakpoints have been mapped by complementation analysis relative to genes on chromosome I. Nineteen duplication breakpoints and seven deficiency breakpoints divide the left half of the chromosome into 24 regions. We have studied the relationship between duplication size and segregational stability. While size is an important determinant of mitotic stability, it is not the only one. We observed clear exceptions to a size-stability correlation. In addition to size, duplication stability may be influenced by specific sequences or chromosome structure. The majority of the duplications were stable enough to be powerful tools for gene mapping. Therefore the duplications described here will be useful in the genetic characterization of chromosome I and the techniques we have developed can be adapted to other regions of the genome.

  4. Physical maps and recombination frequency of six rice chromosomes.

    Science.gov (United States)

    Wu, Jianzhong; Mizuno, Hiroshi; Hayashi-Tsugane, Mika; Ito, Yukiyo; Chiden, Yoshino; Fujisawa, Masaki; Katagiri, Satoshi; Saji, Shoko; Yoshiki, Shoji; Karasawa, Wataru; Yoshihara, Rie; Hayashi, Akiko; Kobayashi, Harumi; Ito, Kazue; Hamada, Masao; Okamoto, Masako; Ikeno, Maiko; Ichikawa, Yoko; Katayose, Yuichi; Yano, Masahiro; Matsumoto, Takashi; Sasaki, Takuji

    2003-12-01

    We constructed physical maps of rice chromosomes 1, 2, and 6-9 with P1-derived artificial chromosome (PAC) and bacterial artificial chromosome (BAC) clones. These maps, with only 20 gaps, cover more than 97% of the predicted length of the six chromosomes. We submitted a total of 193 Mbp of non-overlapping sequences to public databases. We analyzed the DNA sequences of 1316 genetic markers and six centromere-specific repeats to facilitate characterization of chromosomal recombination frequency and of the genomic composition and structure of the centromeric regions. We found marked changes in the relative recombination rate along the length of each chromosome. Chromosomal recombination at the centromere core and surrounding regions on the six chromosomes was completely suppressed. These regions have a total physical length of about 23 Mbp, corresponding to 11.4% of the entire size of the six chromosomes. Chromosome 6 has the longest quiescent region, with about 5.6 Mbp, followed by chromosome 8, with quiescent region about half this size. Repetitive sequences accounted for at least 40% of the total genomic sequence on the partly sequenced centromeric region of chromosome 1. Rice CentO satellite DNA is arrayed in clusters and is closely associated with the presence of Centromeric Retrotransposon of Rice (CRR)- and RIce RetroElement 7 (RIRE7)-like retroelement sequences. We also detected relatively small coldspot regions outside the centromeric region; their repetitive content and gene density were similar to those of regions with normal recombination rates. Sequence analysis of these regions suggests that either the amount or the organization patterns of repetitive sequences may play a role in the inactivation of recombination.

  5. Analysis of chromosome conservation in Lemur catta studied by chromosome paints and BAC/PAC probes.

    Science.gov (United States)

    Cardone, Maria Francesca; Ventura, Mario; Tempesta, Sergio; Rocchi, Mariano; Archidiacono, Nicoletta

    2002-12-01

    A panel of human chromosome painting probes and bacterial and P1 artificial chromosome (BAC/PAC) clones were used in fluorescence in situ hybridization (FISH) experiments to investigate the chromosome conservation of the ring-tailed lemur (Lemur catta, LCA) with respect to human. Whole chromosome paints specific for human chromosomes 7, 9, 11, 13, 14, 17, 18, 20, 21, and X were found to identify a single chromosome or an uninterrupted chromosomal region in LCA. A large set of partial chromosome paints and BAC/PAC probes were then used to refine the characterization of the rearrangements differentiating the two karyotypes. The results were also used to reconstruct the ancestral Lemuridae karyotype. Lemur catta, indeed, can be used as an outgroup, allowing symplesiomorphic (ancestral) rearrangements to be distinguished from apomorphic (derived) rearrangements in lemurs. Some LCA chromosomes are difficult to distinguish morphologically. The 'anchorage' of most LCA chromosomes to specific probes will contribute to the standardization of the karyotype of this species.

  6. Comparative genetic mapping revealed powdery mildew resistance gene MlWE4 derived from wild emmer is located in same genomic region of Pm36 and Ml3D232 on chromosome 5BL

    Institute of Scientific and Technical Information of China (English)

    ZHANG Dong; WANG Yong; CHEN Yong-xing; LIU Zhi-yong; OUYANG Shu-hong; WANG Li-li; CUI Yu; WU Qiu-hong; LIANG Yong; WANG Zhen-zhong; XIE Jing-zhong; ZHANG De-yun

    2015-01-01

    Powdery mildew, caused by Blumeria graminis f. sp. tritici, is one of the most devastating wheat diseases. Wild emmer wheat (Triticum turgidum ssp. dicoccoides) is a promising source of disease resistance for wheat. A powdery mildew resistance gene conferring resistance to B. graminis f. sp. tritici isolate E09, originating from wild emmer wheat, has been transferred into the hexaploid wheat line WE4 through crossing and backcrossing. Genetic analyses indicated that the powdery mildew resistance was control ed by a single dominant gene, temporarily designated MlWE4. By mean of comparative genomics and bulked segregant analysis, a genetic linkage map of MlWE4 was constructed, and MlWE4 was mapped on the distal region of chromosome arm 5BL. Comparative genetic linkage maps showed that genes MlWE4, Pm36 and Ml3D232 were co-segregated with markers XBD37670 and XBD37680, indicating they are likely the same gene or al eles in the same locus. The co-segregated markers provide a starting point for chromosome landing and map-based cloning of MlWE4, Pm36 and Ml3D232.

  7. Temporal genomic evolution of bird sex chromosomes

    DEFF Research Database (Denmark)

    Wang, Zongji; Zhang, Jilin; Yang, Wei;

    2014-01-01

    BACKGROUND: Sex chromosomes exhibit many unusual patterns in sequence and gene expression relative to autosomes. Birds have evolved a female heterogametic sex system (male ZZ, female ZW), through stepwise suppression of recombination between chrZ and chrW. To address the broad patterns and complex...... driving forces of Z chromosome evolution, we analyze here 45 newly available bird genomes and four species' transcriptomes, over their course of recombination loss between the sex chromosomes. RESULTS: We show Z chromosomes in general have a significantly higher substitution rate in introns and synonymous...... changes with that of introns, between chrZ and autosomes or regions with increasing ages of becoming Z-linked, therefore codon usage bias in birds is probably driven by the mutational bias. On the other hand, Z chromosomes also evolve significantly faster at nonsynonymous sites relative to autosomes...

  8. Paternal isodisomy of chromosome 6 in association with a maternal supernumerary marker chromosome (6)

    Energy Technology Data Exchange (ETDEWEB)

    James, R.S.; Crolla, J.A.; Sitch, F.L. [Salisbury District Hospital, Wiltshire (United Kingdom)] [and others

    1994-09-01

    Uniparental disomy may arise by a number of different mechanisms of aneuploidy correction. A population that has been identified as being at increased risk of aneuploidy are those individuals bearing supernumerary marker chromosomes (SMCs). There have been a number of cases reported of trisomy 21 in association with bi-satellited marker chromosomes have described two individuals with small inv dup (15) markers. One had paternal isodisomy of chromosome 15 and Angelman syndrome. The other had maternal heterodisomy (15) and Prader-Willi syndrome. At the Wessex Regional Genetics Laboratory we have conducted a search for uniparental disomy of the normal homologues of the chromosomes from which SMCs originated. Our study population consists of 39 probands with SMCs originating from a number of different autosomes, including 17 with SMCs of chromosome 15 origin. Using PCR amplification of microsatellite repeat sequences located distal to the regions included in the SMCs we have determined the parental origin of the two normal homologues in each case. We have identified paternal isodisomy of chromosome 6 in a female child with a supernumerary marker ring chromosome 6 in approximately 70% of peripheral blood lymphocytes. The marker was found to be of maternal origin. This is the second case of paternal isodisomy of chromosome 6 to be reported, and the first in association with a SMC resulting in a partial trisomy for a portion of the short arm of chromosome 6. In spite of this, the patient appears to be functioning appropriately for her age.

  9. Y chromosome AZF region microdeletions in infertile males in south China%中国南方地区不育男性Y染色体AZF区域微缺失分析

    Institute of Scientific and Technical Information of China (English)

    李崎; 周繇; 马宁; 卢伟英; 徐雯; 马燕琳

    2014-01-01

    Objective To detect and analyze the microdeletions of Y chromosome Azoospermia factor (AZF) region in infertile males in South China. Methods A total of 1 152 infertile males with azoospermia and oligo-zoospermia from Reproductive Medicine Center of the Affiliated Hospital of Hainan Medical University were enrolled and tested for microdeletions of AZFa, AZFb, AZFc and AZFd regions in Y chromosome. Eighteen sets of STS primers were selected and divided to four groups for multiplex polymerase chain reaction (PCR) to determine Y-chromosome microdeletions. Blank controls and positive controls (healthy male's DNA) were included in every PCR experiment. Results Among the 1 152 patients, 67 (5.8%) were found at least one microdeletion in AZF regions, including 13 cas-es of azoospermia, 1 case of asthenozoospermia, 7 cases of oligozoospermia and 46 cases of severe oligozoospermia. Sixty patients had deletions in two AZF regions:AZFc combined with AZFd or AZFb combined with AZFd. One patient had deletions in three AZF regions:AZFc combined with AZFb and AZFd. The rates of deletions were 1.49%(1/67) for AZFa, 4.48%(3/67) for AZFb, 92.54%(62/67) for AZFc, and 95.52%(64/67) for AZFd. Conclusion Multiplex PCR is a fast, simple and convenient way to analyze Y chromosome microdeletions, which could help us to understand the real cause of male infertility and provide advice for choosing ART strategy.%目的:检测并分析中国南方地区不育男性Y染色体上无精症因子(Azoospermia factor,AZF)区域的微缺失情况。方法运用多重PCR技术选用18个STS位点分为四组,设置空白对照,并采用正常男性DNA标本为阳性对照,筛查在海南医学院附属医院生殖医学中心就诊的1152例诊断为无精、少精及弱精男性的AZFa、AZFb、AZFc和AZFd 4个区域的微缺失情况。结果1152例男性患者中共检出67例AZF微缺失,缺失率为5.8%;其中,无精症13例,弱精症1例,少精症7例,严重少精症46

  10. The molecular characterization of maize B chromosome specific AFLPs

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The origin and evolution of B chromosomes could be explained by the specific DNA sequence on them.But the specific sequences known were quite limited. To investigate maize B chromosome sqicific DNA sequeces, maize genomes with and without B chromosomes were analyzed by AFLP. Only 5 markers were found specific to genomes with B chromosomes among about 2000 AFLP markers. Southern hybridization and sequence analysis revealed that only the sequence of M8-2D was a B chromosome specific sequence.This sequence contained the telomeric repeat unit AGGGTTT conserved in plant chromosome telomeres.In addition, the sequence of M8-2D shared low homology to clones from maize chromosome 4 centromere as well. M8-2D were localized to B chromosome centromeric and telomeric regions.

  11. Genome size, karyotype polymorphism and chromosomal evolution in Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Renata T Souza

    Full Text Available BACKGROUND: The Trypanosoma cruzi genome was sequenced from a hybrid strain (CL Brener. However, high allelic variation and the repetitive nature of the genome have prevented the complete linear sequence of chromosomes being determined. Determining the full complement of chromosomes and establishing syntenic groups will be important in defining the structure of T. cruzi chromosomes. A large amount of information is now available for T. cruzi and Trypanosoma brucei, providing the opportunity to compare and describe the overall patterns of chromosomal evolution in these parasites. METHODOLOGY/PRINCIPAL FINDINGS: The genome sizes, repetitive DNA contents, and the numbers and sizes of chromosomes of nine strains of T. cruzi from four lineages (TcI, TcII, TcV and TcVI were determined. The genome of the TcI group was statistically smaller than other lineages, with the exception of the TcI isolate Tc1161 (José-IMT. Satellite DNA content was correlated with genome size for all isolates, but this was not accompanied by simultaneous amplification of retrotransposons. Regardless of chromosomal polymorphism, large syntenic groups are conserved among T. cruzi lineages. Duplicated chromosome-sized regions were identified and could be retained as paralogous loci, increasing the dosage of several genes. By comparing T. cruzi and T. brucei chromosomes, homologous chromosomal regions in T. brucei were identified. Chromosomes Tb9 and Tb11 of T. brucei share regions of syntenic homology with three and six T. cruzi chromosomal bands, respectively. CONCLUSIONS: Despite genome size variation and karyotype polymorphism, T. cruzi lineages exhibit conservation of chromosome structure. Several syntenic groups are conserved among all isolates analyzed in this study. The syntenic regions are larger than expected if rearrangements occur randomly, suggesting that they are conserved owing to positive selection. Mapping of the syntenic regions on T. cruzi chromosomal bands

  12. A genome-wide association study identifies a region at chromosome 12 as a potential susceptibility locus for restenosis after percutaneous coronary intervention

    Science.gov (United States)

    Sampietro, M. Lourdes; Trompet, Stella; Verschuren, Jeffrey J.W.; Talens, Rudolf P.; Deelen, Joris; Heijmans, Bastiaan T.; de Winter, Robbert J.; Tio, Rene A.; Doevendans, Pieter A.F.M.; Ganesh, Santhi K.; Nabel, Elizabeth G.; Westra, Harm-Jan; Franke, Lude; van den Akker, Erik B.; Westendorp, Rudi G.J.; Zwinderman, Aeilko H.; Kastrati, Adnan; Koch, Werner; Slagboom, P.Eline; de Knijff, Peter; Jukema, J. Wouter

    2011-01-01

    Percutaneous coronary intervention (PCI) has become an effective therapy to treat obstructive coronary artery diseases (CAD). However, one of the major drawbacks of PCI is the occurrence of restenosis in 5–25% of all initially treated patients. Restenosis is defined as the re-narrowing of the lumen of the blood vessel, resulting in renewed symptoms and the need for repeated intervention. To identify genetic variants that are associated with restenosis, a genome-wide association study (GWAS) was conducted in 295 patients who developed restenosis (cases) and 571 who did not (controls) from the GENetic Determinants of Restenosis (GENDER) study. Analysis of ∼550 000 single nucleotide polymorphisms (SNPs) in GENDER was followed by a replication phase in three independent case–control populations (533 cases and 3067 controls). A potential susceptibility locus for restenosis at chromosome 12, including rs10861032 (Pcombined = 1.11 × 10−7) and rs9804922 (Pcombined = 1.45 × 10−6), was identified in the GWAS and replication phase. In addition, both SNPs were also associated with coronary events (rs10861032, Padditive = 0.005; rs9804922, Padditive = 0.023) in a trial based cohort set of elderly patients with (enhanced risk of) CAD (PROSPER) and all-cause mortality in PROSPER (rs10861032, Padditive = 0.007; rs9804922, Padditive = 0.013) and GENDER (rs10861032, Padditive = 0.005; rs9804922, Padditive = 0.023). Further analysis suggests that this locus could be involved in regulatory functions. PMID:21878436

  13. Neocentrics and holokinetics (holocentrics): chromosomes out of the centromeric rules.

    Science.gov (United States)

    Guerra, M; Cabral, G; Cuacos, M; González-García, M; González-Sánchez, M; Vega, J; Puertas, M J

    2010-07-01

    The centromere appears as a single constriction at mitotic metaphase in most eukaryotic chromosomes. Holokinetic chromosomes are the exception to this rule because they do not show any centromeric constrictions. Holokinetic chromosomes are usually forgotten in most reviews about centromeres, despite their presence in a number of animal and plant species. They are generally linked to very intriguing and unusual mechanisms of mitosis and meiosis. Holokinetic chromosomes differ from monocentric chromosomes not only in the extension of the kinetochore plate, but also in many other peculiar karyological features, which could be understood as the 'holokinetic syndrome' that is reviewed in detail. Together with holokinetic chromosomes we review neocentromeric activity, a similarly intriguing case of regions able to pull chromosomes towards the poles without showing the main components reported to be essential to centromeric function. A neocentromere is a chromosomal region different from the true centromere in structure, DNA sequence and location, but is able to lead chromosomes to the cell poles in special circumstances. Neocentromeres have been reported in plants and animals showing different features. Both in humans and Drosophila, neocentric activity appears in somatic cells with defective chromosomes lacking a functional centromere. In most cases in plants, neocentromeres appear in chromosomes which have normal centromeres, but are active only during meiosis. Because of examples such as spontaneous or induced neocentromeres and holokinetic chromosomes, it is becoming less surprising that different structures and DNA sequences of centromeres appear in evolution.

  14. Engineering of plant chromosomes.

    Science.gov (United States)

    Mette, Michael Florian; Houben, Andreas

    2015-02-01

    Engineered minimal chromosomes with sufficient mitotic and meiotic stability have an enormous potential as vectors for stacking multiple genes required for complex traits in plant biotechnology. Proof of principle for essential steps in chromosome engineering such as truncation of chromosomes by T-DNA-mediated telomere seeding and de novo formation of centromeres by cenH3 fusion protein tethering has been recently obtained. In order to generate robust protocols for application in plant biotechnology, these steps need to be combined and supplemented with additional methods such as site-specific recombination for the directed transfer of multiple genes of interest on the minichromosomes. At the same time, the development of these methods allows new insight into basic aspects of plant chromosome functions such as how centromeres assure proper distribution of chromosomes to daughter cells or how telomeres serve to cap the chromosome ends to prevent shortening of ends over DNA replication cycles and chromosome end fusion.

  15. Meiotic chromosomes and stages of sex chromosome evolution in fish: zebrafish, platyfish and guppy.

    Science.gov (United States)

    Traut, W; Winking, H

    2001-01-01

    We describe SC complements and results from comparative genomic hybridization (CGH) on mitotic and meiotic chromosomes of the zebrafish Danio rerio, the platyfish Xiphophorus maculatus and the guppy Poecilia reticulata. The three fish species represent basic steps of sex chromosome differentiation: (1) the zebrafish with an all-autosome karyotype; (2) the platyfish with genetically defined sex chromosomes but no differentiation between X and Y visible in the SC or with CGH in meiotic and mitotic chromosomes; (3) the guppy with genetically and cytogenetically differentiated sex chromosomes. The acrocentric Y chromosomes of the guppy consists of a proximal homologous and a distal differential segment. The proximal segment pairs in early pachytene with the respective X chromosome segment. The differential segment is unpaired in early pachytene but synapses later in an 'adjustment' or 'equalization' process. The segment includes a postulated sex determining region and a conspicuous variable heterochromatic region whose structure depends on the particular Y chromosome line. CGH differentiates a large block of predominantly male-specific repetitive DNA and a block of common repetitive DNA in that region.

  16. Chromosomal organization and segregation in Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Isabelle Vallet-Gely

    2013-05-01

    Full Text Available The study of chromosomal organization and segregation in a handful of bacteria has revealed surprising variety in the mechanisms mediating such fundamental processes. In this study, we further emphasized this diversity by revealing an original organization of the Pseudomonas aeruginosa chromosome. We analyzed the localization of 20 chromosomal markers and several components of the replication machinery in this important opportunistic γ-proteobacteria pathogen. This technique allowed us to show that the 6.3 Mb unique circular chromosome of P. aeruginosa is globally oriented from the old pole of the cell to the division plane/new pole along the oriC-dif axis. The replication machinery is positioned at mid-cell, and the chromosomal loci from oriC to dif are moved sequentially to mid-cell prior to replication. The two chromosomal copies are subsequently segregated at their final subcellular destination in the two halves of the cell. We identified two regions in which markers localize at similar positions, suggesting a bias in the distribution of chromosomal regions in the cell. The first region encompasses 1.4 Mb surrounding oriC, where loci are positioned around the 0.2/0.8 relative cell length upon segregation. The second region contains at least 800 kb surrounding dif, where loci show an extensive colocalization step following replication. We also showed that disrupting the ParABS system is very detrimental in P. aeruginosa. Possible mechanisms responsible for the coordinated chromosomal segregation process and for the presence of large distinctive regions are discussed.

  17. Transposable elements and early evolution of sex chromosomes in fish.

    Science.gov (United States)

    Chalopin, Domitille; Volff, Jean-Nicolas; Galiana, Delphine; Anderson, Jennifer L; Schartl, Manfred

    2015-09-01

    In many organisms, the sex chromosome pair can be recognized due to heteromorphy; the Y and W chromosomes have often lost many genes due to the absence of recombination during meiosis and are frequently heterochromatic. Repetitive sequences are found at a high proportion on such heterochromatic sex chromosomes and the evolution and emergence of sex chromosomes has been connected to the dynamics of repeats and transposable elements. With an amazing plasticity of sex determination mechanisms and numerous instances of independent emergence of novel sex chromosomes, fish represent an excellent lineage to investigate the early stages of sex chromosome differentiation, where sex chromosomes often are homomorphic and not heterochromatic. We have analyzed the composition, distribution, and relative age of TEs from available sex chromosome sequences of seven teleost fish. We observed recent bursts of TEs and simple repeat accumulations around young sex determination loci. More strikingly, we detected transposable element (TE) amplifications not only on the sex determination regions of the Y and W sex chromosomes, but also on the corresponding regions of the X and Z chromosomes. In one species, we also clearly demonstrated that the observed TE-rich sex determination locus originated from a TE-poor genomic region, strengthening the link between TE accumulation and emergence of the sex determination locus. Altogether, our results highlight the role of TEs in the initial steps of differentiation and evolution of sex chromosomes.

  18. Sub-megabase resolution tiling (SMRT array-based comparative genomic hybridization profiling reveals novel gains and losses of chromosomal regions in Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma cell lines

    Directory of Open Access Journals (Sweden)

    Lam Wan L

    2008-01-01

    Full Text Available Abstract Background Hodgkin lymphoma (HL and Anaplastic Large Cell Lymphoma (ALCL, are forms of malignant lymphoma defined by unique morphologic, immunophenotypic, genotypic, and clinical characteristics, but both overexpress CD30. We used sub-megabase resolution tiling (SMRT array-based comparative genomic hybridization to screen HL-derived cell lines (KMH2 and L428 and ALCL cell lines (DEL and SR-786 in order to identify disease-associated gene copy number gains and losses. Results Significant copy number gains and losses were observed on several chromosomes in all four cell lines. Assessment of copy number alterations with 26,819 DNA segments identified an average of 20 genetic alterations. Of the recurrent minimally altered regions identified, 11 (55% were within previously published regions of chromosomal alterations in HL and ALCL cell lines while 9 (45% were novel alterations not previously reported. HL cell lines L428 and KMH2 shared gains in chromosome cytobands 2q23.1-q24.2, 7q32.2-q36.3, 9p21.3-p13.3, 12q13.13-q14.1, and losses in 13q12.13-q12.3, and 18q21.32-q23. ALCL cell lines SR-786 and DEL, showed gains in cytobands 5p15.32-p14.3, 20p12.3-q13.11, and 20q13.2-q13.32. Both pairs of HL and ALCL cell lines showed losses in 18q21.32-18q23. Conclusion This study is considered to be the first one describing HL and ALCL cell line genomes at sub-megabase resolution. This high-resolution analysis allowed us to propose novel candidate target genes that could potentially contribute to the pathogenesis of HL and ALCL. FISH was used to confirm the amplification of all three isoforms of the trypsin gene (PRSS1/PRSS2/PRSS3 in KMH2 and L428 (HL and DEL (ALCL cell lines. These are novel findings that have not been previously reported in the lymphoma literature, and opens up an entirely new area of research that has not been previously associated with lymphoma biology. The findings raise interesting possibilities about the role of signaling

  19. The mating type locus (MAT and sexual reproduction of Cryptococcus heveanensis: insights into the evolution of sex and sex-determining chromosomal regions in fungi.

    Directory of Open Access Journals (Sweden)

    Banu Metin

    2010-05-01

    transitions in sexuality concomitant with emergence of a pathogenic clade. These studies provide insight into convergent processes that independently punctuated evolution of sex-determining loci and sex chromosomes in fungi, plants, and animals.

  20. Two mutations in the locus control region hypersensitivity site-2 (5' HS-2) of haplotype 19 beta s chromosomes alter binding of trans-acting factors.

    Science.gov (United States)

    Morgan, J C; Scott, D F; Lanclos, K D

    1996-01-01

    There are five major haplotypes associated with sickle cell anemia (SS). Individuals homozygous for haplotypes 3 (Senegal) and 31 (Saudi Arabian) have high fetal hemoglobin (HbF) levels (15 to 30% of total hemoglobin) whereas individuals homozygous for haplotypes 17 (Cameroon), 19 (Benin), and 20 (Bantu) have low HbF levels (1 to 10%). We previously identified several point mutations in the LCR 5'HS-2 that were specific for haplotype 19 beta s chromosomes (compared to the GenBank HUMHBB reference sequence, T-->G at position 8580, A-->G at position 8598, and A-->T at position 9114). We postulated that one or more of these mutations may alter the binding of specific trans-acting factors and ultimately affect the expression of HbF in these sickle cell patients. We performed gel mobility shift assays using 32P-end-labeled double-stranded 19mers corresponding to each of the LCR 5'HS-2 normal (GenBank) and mutant sequences. Nuclear extracts prepared from HeLa and HEL cells were used in our experiments and neither the normal nor mutant sequence at position 8580 bound trans-acting factors in either nuclear extract. The 8598 mutant increased binding of Sp1; using purified protein and both nuclear extracts. HEL extracts were used to quantify the increase in Sp1 binding to the 8598 mutation and we found an increase in binding of 66 and 47%, respectively, in two shifted bands. The 9114 mutation sharply decreased binding of an unknown trans-acting factor by 74%. This factor was present in both HeLa and HEL nuclear extracts.

  1. Chromosomal instability in meningiomas.

    Science.gov (United States)

    van Tilborg, Angela A G; Al Allak, Bushra; Velthuizen, Sandra C J M; de Vries, Annie; Kros, Johan M; Avezaat, Cees J J; de Klein, Annelies; Beverloo, H Berna; Zwarthoff, Ellen C

    2005-04-01

    Approximately 60% of sporadic meningiomas are caused by inactivation of the NF2 tumor suppressor gene on chromosome 22. No causative gene is known for the remaining 40%. Cytogenetic analysis shows that meningiomas caused by inactivation of the NF2 gene can be divided into tumors that show monosomy 22 as the sole abnormality and tumors with a more complex karyotype. Meningiomas not caused by the NF2 gene usually have a diploid karyotype. Here we report that, besides the clonal chromosomal aberrations, the chromosome numbers in many meningiomas varied from one metaphase spread to the other, a feature that is indicative of chromosomal instability. Unexpectedly and regardless of genotype, a subgroup of tumors was observed with an average number of 44.9 chromosomes and little variation in the number of chromosomes per metaphase spread. In addition, a second subgroup was recognized with a hyperdiploid number of chromosomes (average 48.5) and considerable variation in numbers per metaphase. However, this numerical instability resulted in a clonal karyotype with chromosomal gains and losses in addition to loss of chromosome 22 only in meningiomas caused by inactivation of the NF2 gene. In cultured cells of all tumor groups, bi- and multinucleated cells were seen, as well as anaphase bridges, residual chromatid strings, multiple spindle poles, and unseparated chromatids, suggesting defects in the mitotic apparatus or kinetochore. Thus, we conclude that even a benign and slow-growing tumor like a meningioma displays chromosomal instability.

  2. Homomorphic sex chromosomes and the intriguing Y chromosome of Ctenomys rodent species (Rodentia, Ctenomyidae).

    Science.gov (United States)

    Suárez-Villota, Elkin Y; Pansonato-Alves, José C; Foresti, Fausto; Gallardo, Milton H

    2014-01-01

    Unlike the X chromosome, the mammalian Y chromosome undergoes evolutionary decay resulting in small size. This sex chromosomal heteromorphism, observed in most species of the fossorial rodent Ctenomys, contrasts with the medium-sized, homomorphic acrocentric sex chromosomes of closely related C. maulinus and C. sp. To characterize the sequence composition of these chromosomes, fluorescent banding, self-genomic in situ hybridization, and fluorescent in situ hybridization with an X painting probe were performed on mitotic and meiotic plates. High molecular homology between the sex chromosomes was detected on mitotic material as well as on meiotic plates immunodetected with anti-SYCP3 and anti-γH2AX. The Y chromosome is euchromatic, poor in repetitive sequences and differs from the X by the loss of a block of pericentromeric chromatin. Inferred from the G-banding pattern, an inversion and the concomitant prevention of recombination in a large asynaptic region seems to be crucial for meiotic X chromosome inactivation. These peculiar findings together with the homomorphism of Ctenomys sex chromosomes are discussed in the light of the regular purge that counteracts Muller's ratchet and the probable mechanisms accounting for their origin and molecular homology.

  3. Selection and mapping of replication origins from a 500-kb region of the human X chromosome and their relationship to gene expression.

    Science.gov (United States)

    Rivella, S; Palermo, B; Pelizon, C; Sala, C; Arrigo, G; Toniolo, D

    1999-11-15

    In higher eukaryotes the mechanism controlling initiation of DNA replication remains largely unknown. New technologies are needed to shed light on how DNA replication initiates along the genome in specific regions. To identify the human DNA sequence requirements for initiation of replication, we developed a new method that allows selection of replication origins starting from large genomic regions of human DNA. We repeatedly isolated 15 new putative replication origins (PROs) from a human DNA region of 500 kb in which 17 genes have previously been characterized. Fine-mapping of these PROs showed that DNA replication can initiate at many specific points along actively transcribed DNA in the cell lines used for our selection. In conclusion, in this paper we describe a new method to identify PROs that suggests that the availability of initiation sites is dependent on the transcriptional state of the DNA.

  4. Rapid evolutionary dynamics in a 2.8-Mb chromosomal region containing multiple prolamin and resistance gene families in Aegilops tauschii.

    Science.gov (United States)

    Dong, Lingli; Huo, Naxin; Wang, Yi; Deal, Karin; Wang, Daowen; Hu, Tiezhu; Dvorak, Jan; Anderson, Olin D; Luo, Ming-Cheng; Gu, Yong Q

    2016-09-01

    Prolamin and resistance gene families are important in wheat food use and in defense against pathogen attacks, respectively. To better understand the evolution of these multi-gene families, the DNA sequence of a 2.8-Mb genomic region, representing an 8.8 cM genetic interval and harboring multiple prolamin and resistance-like gene families, was analyzed in the diploid grass Aegilops tauschii, the D-genome donor of bread wheat. Comparison with orthologous regions from rice, Brachypodium, and sorghum showed that the Ae. tauschii region has undergone dramatic changes; it has acquired more than 80 non-syntenic genes and only 13 ancestral genes are shared among these grass species. These non-syntenic genes, including prolamin and resistance-like genes, originated from various genomic regions and likely moved to their present locations via sequence evolution processes involving gene duplication and translocation. Local duplication of non-syntenic genes contributed significantly to the expansion of gene families. Our analysis indicates that the insertion of prolamin-related genes occurred prior to the separation of the Brachypodieae and Triticeae lineages. Unlike in Brachypodium, inserted prolamin genes have rapidly evolved and expanded to encode different classes of major seed storage proteins in Triticeae species. Phylogenetic analyses also showed that the multiple insertions of resistance-like genes and subsequent differential expansion of each R gene family. The high frequency of non-syntenic genes and rapid local gene evolution correlate with the high recombination rate in the 2.8-Mb region with nine-fold higher than the genome-wide average. Our results demonstrate complex evolutionary dynamics in this agronomically important region of Triticeae species.

  5. Solvability of the Diophantine equations xp + 22m y4 = pk z2 and xp + y2 = pk z4

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    We study the solvability of two classes of Diophantine equations by using some new methods and new results in this paper.Letp be an odd prime and Bn denote nth Bernoulli number.We prove that ifp ≡ 1(mod 4)andp |B(p-1)/2,then the equationxp +22mn4 = pky2,m,n,k ∈ N ,k > 1,gcd(x,py)= 1,and the equationxp +y2 =pkz4,k ∈ N,gcd(x,y)= 1,k > 1,21 y have no integral solutions respectively.

  6. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33

    Science.gov (United States)

    Wang, Zhaoming; Zhu, Bin; Zhang, Mingfeng; Parikh, Hemang; Jia, Jinping; Chung, Charles C.; Sampson, Joshua N.; Hoskins, Jason W.; Hutchinson, Amy; Burdette, Laurie; Ibrahim, Abdisamad; Hautman, Christopher; Raj, Preethi S.; Abnet, Christian C.; Adjei, Andrew A.; Ahlbom, Anders; Albanes, Demetrius; Allen, Naomi E.; Ambrosone, Christine B.; Aldrich, Melinda; Amiano, Pilar; Amos, Christopher; Andersson, Ulrika; Andriole, Gerald; Andrulis, Irene L.; Arici, Cecilia; Arslan, Alan A.; Austin, Melissa A.; Baris, Dalsu; Barkauskas, Donald A.; Bassig, Bryan A.; Beane Freeman, Laura E.; Berg, Christine D.; Berndt, Sonja I.; Bertazzi, Pier Alberto; Biritwum, Richard B.; Black, Amanda; Blot, William; Boeing, Heiner; Boffetta, Paolo; Bolton, Kelly; Boutron-Ruault, Marie-Christine; Bracci, Paige M.; Brennan, Paul; Brinton, Louise A.; Brotzman, Michelle; Bueno-de-Mesquita, H. Bas; Buring, Julie E.; Butler, Mary Ann; Cai, Qiuyin; Cancel-Tassin, Geraldine; Canzian, Federico; Cao, Guangwen; Caporaso, Neil E.; Carrato, Alfredo; Carreon, Tania; Carta, Angela; Chang, Gee-Chen; Chang, I-Shou; Chang-Claude, Jenny; Che, Xu; Chen, Chien-Jen; Chen, Chih-Yi; Chen, Chung-Hsing; Chen, Constance; Chen, Kuan-Yu; Chen, Yuh-Min; Chokkalingam, Anand P.; Chu, Lisa W.; Clavel-Chapelon, Francoise; Colditz, Graham A.; Colt, Joanne S.; Conti, David; Cook, Michael B.; Cortessis, Victoria K.; Crawford, E. David; Cussenot, Olivier; Davis, Faith G.; De Vivo, Immaculata; Deng, Xiang; Ding, Ti; Dinney, Colin P.; Di Stefano, Anna Luisa; Diver, W. Ryan; Duell, Eric J.; Elena, Joanne W.; Fan, Jin-Hu; Feigelson, Heather Spencer; Feychting, Maria; Figueroa, Jonine D.; Flanagan, Adrienne M.; Fraumeni, Joseph F.; Freedman, Neal D.; Fridley, Brooke L.; Fuchs, Charles S.; Gago-Dominguez, Manuela; Gallinger, Steven; Gao, Yu-Tang; Gapstur, Susan M.; Garcia-Closas, Montserrat; Garcia-Closas, Reina; Gastier-Foster, Julie M.; Gaziano, J. Michael; Gerhard, Daniela S.; Giffen, Carol A.; Giles, Graham G.; Gillanders, Elizabeth M.; Giovannucci, Edward L.; Goggins, Michael; Gokgoz, Nalan; Goldstein, Alisa M.; Gonzalez, Carlos; Gorlick, Richard; Greene, Mark H.; Gross, Myron; Grossman, H. Barton; Grubb, Robert; Gu, Jian; Guan, Peng; Haiman, Christopher A.; Hallmans, Goran; Hankinson, Susan E.; Harris, Curtis C.; Hartge, Patricia; Hattinger, Claudia; Hayes, Richard B.; He, Qincheng; Helman, Lee; Henderson, Brian E.; Henriksson, Roger; Hoffman-Bolton, Judith; Hohensee, Chancellor; Holly, Elizabeth A.; Hong, Yun-Chul; Hoover, Robert N.; Hosgood, H. Dean; Hsiao, Chin-Fu; Hsing, Ann W.; Hsiung, Chao Agnes; Hu, Nan; Hu, Wei; Hu, Zhibin; Huang, Ming-Shyan; Hunter, David J.; Inskip, Peter D.; Ito, Hidemi; Jacobs, Eric J.; Jacobs, Kevin B.; Jenab, Mazda; Ji, Bu-Tian; Johansen, Christoffer; Johansson, Mattias; Johnson, Alison; Kaaks, Rudolf; Kamat, Ashish M.; Kamineni, Aruna; Karagas, Margaret; Khanna, Chand; Khaw, Kay-Tee; Kim, Christopher; Kim, In-Sam; Kim, Jin Hee; Kim, Yeul Hong; Kim, Young-Chul; Kim, Young Tae; Kang, Chang Hyun; Jung, Yoo Jin; Kitahara, Cari M.; Klein, Alison P.; Klein, Robert; Kogevinas, Manolis; Koh, Woon-Puay; Kohno, Takashi; Kolonel, Laurence N.; Kooperberg, Charles; Kratz, Christian P.; Krogh, Vittorio; Kunitoh, Hideo; Kurtz, Robert C.; Kurucu, Nilgun; Lan, Qing; Lathrop, Mark; Lau, Ching C.; Lecanda, Fernando; Lee, Kyoung-Mu; Lee, Maxwell P.; Le Marchand, Loic; Lerner, Seth P.; Li, Donghui; Liao, Linda M.; Lim, Wei-Yen; Lin, Dongxin; Lin, Jie; Lindstrom, Sara; Linet, Martha S.; Lissowska, Jolanta; Liu, Jianjun; Ljungberg, Börje; Lloreta, Josep; Lu, Daru; Ma, Jing; Malats, Nuria; Mannisto, Satu; Marina, Neyssa; Mastrangelo, Giuseppe; Matsuo, Keitaro; McGlynn, Katherine A.; McKean-Cowdin, Roberta; McNeill, Lorna H.; McWilliams, Robert R.; Melin, Beatrice S.; Meltzer, Paul S.; Mensah, James E.; Miao, Xiaoping; Michaud, Dominique S.; Mondul, Alison M.; Moore, Lee E.; Muir, Kenneth; Niwa, Shelley; Olson, Sara H.; Orr, Nick; Panico, Salvatore; Park, Jae Yong; Patel, Alpa V.; Patino-Garcia, Ana; Pavanello, Sofia; Peeters, Petra H. M.; Peplonska, Beata; Peters, Ulrike; Petersen, Gloria M.; Picci, Piero; Pike, Malcolm C.; Porru, Stefano; Prescott, Jennifer; Pu, Xia; Purdue, Mark P.; Qiao, You-Lin; Rajaraman, Preetha; Riboli, Elio; Risch, Harvey A.; Rodabough, Rebecca J.; Rothman, Nathaniel; Ruder, Avima M.; Ryu, Jeong-Seon; Sanson, Marc; Schned, Alan; Schumacher, Fredrick R.; Schwartz, Ann G.; Schwartz, Kendra L.; Schwenn, Molly; Scotlandi, Katia; Seow, Adeline; Serra, Consol; Serra, Massimo; Sesso, Howard D.; Severi, Gianluca; Shen, Hongbing; Shen, Min; Shete, Sanjay; Shiraishi, Kouya; Shu, Xiao-Ou; Siddiq, Afshan; Sierrasesumaga, Luis; Sierri, Sabina; Loon Sihoe, Alan Dart; Silverman, Debra T.; Simon, Matthias; Southey, Melissa C.; Spector, Logan; Spitz, Margaret; Stampfer, Meir; Stattin, Par; Stern, Mariana C.; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael Z.; Stram, Daniel O.; Strom, Sara S.; Su, Wu-Chou; Sund, Malin; Sung, Sook Whan; Swerdlow, Anthony; Tan, Wen; Tanaka, Hideo; Tang, Wei; Tang, Ze-Zhang; Tardon, Adonina; Tay, Evelyn; Taylor, Philip R.; Tettey, Yao; Thomas, David M.; Tirabosco, Roberto; Tjonneland, Anne; Tobias, Geoffrey S.; Toro, Jorge R.; Travis, Ruth C.; Trichopoulos, Dimitrios; Troisi, Rebecca; Truelove, Ann; Tsai, Ying-Huang; Tucker, Margaret A.; Tumino, Rosario; Van Den Berg, David; Van Den Eeden, Stephen K.; Vermeulen, Roel; Vineis, Paolo; Visvanathan, Kala; Vogel, Ulla; Wang, Chaoyu; Wang, Chengfeng; Wang, Junwen; Wang, Sophia S.; Weiderpass, Elisabete; Weinstein, Stephanie J.; Wentzensen, Nicolas; Wheeler, William; White, Emily; Wiencke, John K.; Wolk, Alicja; Wolpin, Brian M.; Wong, Maria Pik; Wrensch, Margaret; Wu, Chen; Wu, Tangchun; Wu, Xifeng; Wu, Yi-Long; Wunder, Jay S.; Xiang, Yong-Bing; Xu, Jun; Yang, Hannah P.; Yang, Pan-Chyr; Yatabe, Yasushi; Ye, Yuanqing; Yeboah, Edward D.; Yin, Zhihua; Ying, Chen; Yu, Chong-Jen; Yu, Kai; Yuan, Jian-Min; Zanetti, Krista A.; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Zhou, Baosen; Mirabello, Lisa; Savage, Sharon A.; Kraft, Peter; Chanock, Stephen J.; Yeager, Meredith; Landi, Maria Terese; Shi, Jianxin; Chatterjee, Nilanjan; Amundadottir, Laufey T.

    2014-01-01

    Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10−39; Region 3: rs2853677, P = 3.30 × 10−36 and PConditional = 2.36 × 10−8; Region 4: rs2736098, P = 3.87 × 10−12 and PConditional = 5.19 × 10−6, Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10−6; and Region 6: rs10069690, P = 7.49 × 10−15 and PConditional = 5.35 × 10−7) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10−18 and PConditional = 7.06 × 10−16). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci. PMID:25027329

  7. Novel gene acquisition on carnivore Y chromosomes.

    Directory of Open Access Journals (Sweden)

    William J Murphy

    2006-03-01

    Full Text Available Despite its importance in harboring genes critical for spermatogenesis and male-specific functions, the Y chromosome has been largely excluded as a priority in recent mammalian genome sequencing projects. Only the human and chimpanzee Y chromosomes have been well characterized at the sequence level. This is primarily due to the presumed low overall gene content and highly repetitive nature of the Y chromosome and the ensuing difficulties using a shotgun sequence approach for assembly. Here we used direct cDNA selection to isolate and evaluate the extent of novel Y chromosome gene acquisition in the genome of the domestic cat, a species from a different mammalian superorder than human, chimpanzee, and mouse (currently being sequenced. We discovered four novel Y chromosome genes that do not have functional copies in the finished human male-specific region of the Y or on other mammalian Y chromosomes explored thus far. Two genes are derived from putative autosomal progenitors, and the other two have X chromosome homologs from different evolutionary strata. All four genes were shown to be multicopy and expressed predominantly or exclusively in testes, suggesting that their duplication and specialization for testis function were selected for because they enhance spermatogenesis. Two of these genes have testis-expressed, Y-borne copies in the dog genome as well. The absence of the four newly described genes on other characterized mammalian Y chromosomes demonstrates the gene novelty on this chromosome between mammalian orders, suggesting it harbors many lineage-specific genes that may go undetected by traditional comparative genomic approaches. Specific plans to identify the male-specific genes encoded in the Y chromosome of mammals should be a priority.

  8. Chromosome repatterning in three representative parrots (Psittaciformes) inferred from comparative chromosome painting.

    Science.gov (United States)

    Nanda, I; Karl, E; Griffin, D K; Schartl, M; Schmid, M

    2007-01-01

    Parrots (order: Psittaciformes) are the most common captive birds and have attracted human fascination since ancient times because of their remarkable intelligence and ability to imitate human speech. However, their genome organization, evolution and genomic relation with other birds are poorly understood. Chromosome painting with DNA probes derived from the flow-sorted macrochromosomes (1-10) of chicken (Gallus gallus, GGA) has been used to identify and distinguish the homoeologous chromosomal segments in three species of parrots, i.e., Agapornis roseicollis (peach-faced lovebird); Nymphicus hollandicus (cockatiel) and Melopsittacus undulatus (budgerigar). The ten GGA macrochromosome paints unequivocally recognize 14 to 16 hybridizing regions delineating the conserved chromosomal segments for the respective chicken macrochromosomes in these representative parrot species. The cross-species chromosome painting results show that, unlike in many other avian karyotypes with high homology to chicken chromosomes, dramatic rearrangements of the macrochromosomes have occurred in parrot lineages. Among the larger GGA macrochromosomes (1-5), chromosomes 1 and 4 are conserved on two chromosomes in all three species. However, the hybridization pattern for GGA 4 in A. roseicollis and M. undulatus is in sharp contrast to the most common pattern known from hybridization of chicken macrochromosome 4 in other avian karyotypes. With the exception of A. roseicollis, chicken chromosomes 2, 3 and 5 hybridized either completely or partially to a single chromosome. In contrast, the smaller GGA macrochromosomes 6, 7 and 8 displayed a complex hybridization pattern: two or three of these macrochromosomes were found to be contiguously arranged on a single chromosome in all three parrot species. Overall, the study shows that translocations and fusions in conjunction with intragenomic rearrangements have played a major role in the karyotype evolution of parrots. Our inter-species chromosome

  9. Analysis of t(9;17)(q33.2;q25.3) chromosomal breakpoint regions and genetic association reveals novel candidate genes for bipolar disorder

    DEFF Research Database (Denmark)

    Rajkumar, A.P.; Christensen, Jane H.; Mattheisen, Manuel

    2015-01-01

    ,856) data. Genetic associations between these disorders and single nucleotide polymorphisms within these breakpoint regions were analysed by BioQ, FORGE, and RegulomeDB programmes. RESULTS: Four protein-coding genes [coding for (endonuclease V (ENDOV), neuronal pentraxin I (NPTX1), ring finger protein 213...

  10. Congenital diaphragmatic hernia and chromosome 15q26: determination of a candidate region by use of fluorescent in situ hybridization and array-based comparative genomic hybridization

    NARCIS (Netherlands)

    M. Klaassens (Merel); C. Wouters (Cokkie); M.F. van Dooren (Marieke); H.J.F.M.M. Eussen (Bert); H. Douben (Hannie); J.E.M.M. de Klein (Annelies); A.T. den Dekker (Alexander); C. Lee; P.K. Donahoe; D. Tibboel (Dick); R-J.H. Galjaard (Robert-Jan); N.N.T. Goemaere (Natascha); B.A. Oostra (Ben); R.R. de Krijger (Ronald); J. Wauters (Jan)

    2005-01-01

    textabstractCongenital diaphragmatic hernia (CDH) has an incidence of 1 in 3,000 births and a high mortality rate (33%-58%). Multifactorial inheritance, teratogenic agents, and genetic abnormalities have all been suggested as possible etiologic factors. To define candidate regions

  11. The Precarious Prokaryotic Chromosome

    OpenAIRE

    Kuzminov, Andrei

    2014-01-01

    Evolutionary selection for optimal genome preservation, replication, and expression should yield similar chromosome organizations in any type of cells. And yet, the chromosome organization is surprisingly different between eukaryotes and prokaryotes. The nuclear versus cytoplasmic accommodation of genetic material accounts for the distinct eukaryotic and prokaryotic modes of genome evolution, but it falls short of explaining the differences in the chromosome organization. I propose that the t...

  12. Deficit of mitonuclear genes on the human X chromosome predates sex chromosome formation.

    Science.gov (United States)

    Dean, Rebecca; Zimmer, Fabian; Mank, Judith E

    2015-01-29

    Two taxa studied to date, the therian mammals and Caenorhabditis elegans, display underrepresentations of mitonuclear genes (mt-N genes, nuclear genes whose products are imported to and act within the mitochondria) on their X chromosomes. This pattern has been interpreted as the result of sexual conflict driving mt-N genes off of the X chromosome. However, studies in several other species have failed to detect a convergent biased distribution of sex-linked mt-N genes, leading to questions over the generality of the role of sexual conflict in shaping the distribution of mt-N genes. Here we tested whether mt-N genes moved off of the therian X chromosome following sex chromosome formation, consistent with the role of sexual conflict, or whether the paucity of mt-N genes on the therian X is a chance result of an underrepresentation on the ancestral regions that formed the X chromosome. We used a synteny-based approach to identify the ancestral regions in the platypus and chicken genomes that later formed the therian X chromosome. We then quantified the movement of mt-N genes on and off of the X chromosome and the distribution of mt-N genes on the human X and ancestral X regions. We failed to find an excess of mt-N gene movement off of the X. The bias of mt-N genes on ancestral therian X chromosomes was also not significantly different from the biases on the human X. Together our results suggest that, rather than conflict driving mt-N genes off of the mammalian X, random biases on chromosomes that formed the X chromosome could explain the paucity of mt-N genes in the therian lineage.

  13. Isolation and characterization of DNA probes for human chromosome 21.

    Science.gov (United States)

    Watkins, P C

    1990-01-01

    A coordinated effort to map and sequence the human genome has recently become a national priority. Chromosome 21, the smallest human chromosome accounting for less than 2% of the human genome, is an attractive model system for developing and evaluating genome mapping technology. Several strategies are currently being explored including the development of chromosome 21 libraries from somatic cell hybrids as reported here, the cloning of chromosome 21 in yeast artificial chromosomes (McCormick et al., 1989b), and the construction of chromosome 21 libraries using chromosome flow-sorting techniques (Fuscoe et al., 1989). This report describes the approaches used to identify DNA probes that are useful for mapping chromosome 21. Probes were successfully isolated from both phage and cosmid libraries made from two somatic cell hybrids that contain human chromosome 21 as the only human chromosome. The 15 cosmid clones from the WA17 library, reduced to cloned DNA sequences of an average size of 3 kb, total 525 kb of DNA which is approximately 1% of chromosome 21. From these clones, a set of polymorphic DNA markers that span the length of the long arm of chromosome 21 has been generated. All of the probes thus far analyzed from the WA17 libraries have been mapped to chromosome 21 both by physical and genetic mapping methods. It is therefore likely that the WA17 hybrid cell line contains human chromosome 21 as the only human component, in agreement with cytogenetic observation. The 153E7b cosmid libraries will provide an alternative source of cloned chromosome 21 DNA. Library screening techniques can be employed to obtain cloned DNA sequences from the same genetic loci of the two different chromosome 21s. Comparative analysis will allow direct estimation of DNA sequence variation for different regions of chromosome 21. Mapped DNA probes make possible the molecular analysis of chromosome 21 at a level of resolution not achievable by classical cytogenetic techniques (Graw et al

  14. Chromosome oscillations in mitosis

    Science.gov (United States)

    Campas, Otger

    2008-03-01

    Successful cell division necessitates a tight regulation of chromosome movement via the activity of molecular motors. Many of the key players at the origin of the forces generating the motion have been identified, but their spatial and temporal organization remains elusive. In animal cells, chromosomes periodically switch between phases of movement towards and away from the pole. This characteristic oscillatory behaviour cannot be explained by the current models of chromosome positioning and congression. We perform a self-contained theoretical analysis in which the motion of mono-oriented chromosomes results from the competition between the activity of the kinetochore and chromokinesin motors on the chromosome arms. Our analysis, consistent with the available experimental data, proposes that the interplay between the aster-like morphology of the spindle and the collective kinetics of molecular motors is at the origin of chromosome oscillations, positioning and congression. It provides a natural explanation for the so-called chromosome directional instability and for the mechanism by which chromosomes sense their position in space. In addition, we estimate the in vivo velocity of chromokinesins at vanishing load and propose new experiments to assess the mechanism at the origin of chromosome movement in cell division.

  15. Bacterial chromosome segregation.

    Science.gov (United States)

    Possoz, Christophe; Junier, Ivan; Espeli, Olivier

    2012-01-01

    Dividing cells have mechanisms to ensure that their genomes are faithfully segregated into daughter cells. In bacteria, the description of these mechanisms has been considerably improved in the recent years. This review focuses on the different aspects of bacterial chromosome segregation that can be understood thanks to the studies performed with model organisms: Escherichia coli, Bacillus subtilis, Caulobacter crescentus and Vibrio cholerae. We describe the global positionning of the nucleoid in the cell and the specific localization and dynamics of different chromosomal loci, kinetic and biophysic aspects of chromosome segregation are presented. Finally, a presentation of the key proteins involved in the chromosome segregation is made.

  16. Origin and domestication of papaya Yh chromosome.

    Science.gov (United States)

    VanBuren, Robert; Zeng, Fanchang; Chen, Cuixia; Zhang, Jisen; Wai, Ching Man; Han, Jennifer; Aryal, Rishi; Gschwend, Andrea R; Wang, Jianping; Na, Jong-Kuk; Huang, Lixian; Zhang, Lingmao; Miao, Wenjing; Gou, Jiqing; Arro, Jie; Guyot, Romain; Moore, Richard C; Wang, Ming-Li; Zee, Francis; Charlesworth, Deborah; Moore, Paul H; Yu, Qingyi; Ming, Ray

    2015-04-01

    Sex in papaya is controlled by a pair of nascent sex chromosomes. Females are XX, and two slightly different Y chromosomes distinguish males (XY) and hermaphrodites (XY(h)). The hermaphrodite-specific region of the Y(h) chromosome (HSY) and its X chromosome counterpart were sequenced and analyzed previously. We now report the sequence of the entire male-specific region of the Y (MSY). We used a BAC-by-BAC approach to sequence the MSY and resequence the Y regions of 24 wild males and the Y(h) regions of 12 cultivated hermaphrodites. The MSY and HSY regions have highly similar gene content and structure, and only 0.4% sequence divergence. The MSY sequences from wild males include three distinct haplotypes, associated with the populations' geographic locations, but gene flow is detected for other genomic regions. The Y(h) sequence is highly similar to one Y haplotype (MSY3) found only in wild dioecious populations from the north Pacific region of Costa Rica. The low MSY3-Y(h) divergence supports the hypothesis that hermaphrodite papaya is a product of human domestication. We estimate that Y(h) arose only ∼ 4000 yr ago, well after crop plant domestication in Mesoamerica >6200 yr ago but coinciding with the rise of the Maya civilization. The Y(h) chromosome has lower nucleotide diversity than the Y, or the genome regions that are not fully sex-linked, consistent with a domestication bottleneck. The identification of the ancestral MSY3 haplotype will expedite investigation of the mutation leading to the domestication of the hermaphrodite Y(h) chromosome. In turn, this mutation should identify the gene that was affected by the carpel-suppressing mutation that was involved in the evolution of males.

  17. The fragile Y hypothesis: Y chromosome aneuploidy as a selective pressure in sex chromosome and meiotic mechanism evolution.

    Science.gov (United States)

    Blackmon, Heath; Demuth, Jeffery P

    2015-09-01

    Loss of the Y-chromosome is a common feature of species with chromosomal sex determination. However, our understanding of why some lineages frequently lose Y-chromosomes while others do not is limited. The fragile Y hypothesis proposes that in species with chiasmatic meiosis the rate of Y-chromosome aneuploidy and the size of the recombining region have a negative correlation. The fragile Y hypothesis provides a number of novel insights not possible under traditional models. Specifically, increased rates of Y aneuploidy may impose positive selection for (i) gene movement off the Y; (ii) translocations and fusions which expand the recombining region; and (iii) alternative meiotic segregation mechanisms (achiasmatic or asynaptic). These insights as well as existing evidence for the frequency of Y-chromosome aneuploidy raise doubt about the prospects for long-term retention of the human Y-chromosome despite recent evidence for stable gene content in older non-recombining regions.

  18. A Narrow and Highly Significant Linkage Signal for Severe Bipolar Disorder in the Chromosome 5q33 Region in Latin American Pedigrees

    Science.gov (United States)

    Jasinska, A.J.; Service, S.; Jawaheer, D.; DeYoung, J.; Levinson, M.; Zhang, Z.; Kremeyer, B.; Muller, H.; Aldana, I.; Garcia, J.; Restrepo, G.; Lopez, C.; Palacio, C.; Duque, C.; Parra, M.; Vega, J.; Ortiz, D.; Bedoya, G.; Mathews, C.; Davanzo, P.; Fournier, E.; Bejarano, J.; Ramirez, M.; Ortiz, C. Araya; Araya, X.; Molina, J.; Sabatti, C.; Reus, V.; Ospina, J.; Macaya, G.; Ruiz-Linares, A.; Freimer, N.B.

    2016-01-01

    We previously reported linkage of bipolar disorder to 5q33-q34 in families from two closely related population isolates, the Central Valley of Costa Rica (CVCR) and Antioquia, Colombia (CO). Here we present follow up results from fine-scale mapping in large CVCR and CO families segregating severe bipolar disorder, BP-I, and in 343 population trios/duos from CVCR and CO. Employing densely spaced SNPs to fine map the prior linkage peak region increases linkage evidence and clarifies the position of the putative BP-I locus. We performed two-point linkage analysis with 1134 SNPs in an appro