A high-resolution genetic linkage map of the pericentromeric region of the human X chromosome

Weeks, Daniel E.; Nygaard, Torbjoern G.; Neystat, M.; Harby, Lisa D.; Wilhelmsen, Kirk C.

doi:10.1016/0888-7543(95)80080-6

Cited by 12 publications

(13 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, these results support the BTX linkage results of Yeh and coworkers (1996) that suggest heterogeneity of recombination for BTX. The observed reduction in recombination near the centromere correlates with that observed for the pericentromeric region of X in humans (Weeks et al 1995). Linkage distances between markers more distally located on BTXp suggest a region of elevated recombination exists between BMS631 and BL1098.…”

Section: ) Marker Order Was Identical To That Reported By Yeh Et Alsupporting

confidence: 58%

An integrated genetic and physical map of the bovine X Chromosome

Sonstegard¹,

Lopez-Corrales²,

Kappes³

et al. 1997

Mammalian Genome

View full text Add to dashboard Cite

Abstract. Genotypic data for 56 microsatellites (ms) generated from maternal full sib families nested within paternal half sib pedigrees were used to construct a linkage map of the bovine X Chromosome (Chr) (BTX) that spans 150 cM (ave. interval 2.7 cM). The linkage map contains 36 previously unlinked ms; seven generated from a BTXp library. Genotypic data from these 36 ms was merged into an existing linkage map to more than double the number of informative BTX markers. A male specific linkage map of the pseudoautosomal region was also constructed from five ms at the distal end of BTXq. Four informative probes physically assigned by fluorescence in situ hybridization defined the extent of coverage, confirmed the position of the pseudoautosomal region on the q-arm, and identified a 4.1-cM marker interval containing the centromere of BTX.

show abstract

Section: ) Marker Order Was Identical To That Reported By Yeh Et Alsupporting

confidence: 58%

An integrated genetic and physical map of the bovine X Chromosome

Sonstegard¹,

Lopez-Corrales²,

Kappes³

et al. 1997

Mammalian Genome

View full text Add to dashboard Cite

show abstract

“…In patient GT88/6327 the multiplex PCR suggested the presence of a large deletion encompassing all of the ED1 gene and the flanking markers DXS1689 and DXS 1690, indicating that the deletion is at least 2.6 Mb long. 11,20 We observed a splice site variant in the donor site of exon 8 (1166+6T4C in family DK48/900). Although this variant was not found in more than 120 normal X-chromosomes, it is of uncertain pathogenic significance as the transcript analysis could not be performed.…”

Section: Mutational Spectrummentioning

confidence: 98%

Mutational spectrum of the ED1 gene in X-linked hypohidrotic ectodermal dysplasia

et al. 2001

View full text Add to dashboard Cite

X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common form of the ectodermal dysplasias characterised by an abnormal development of eccrine sweat glands, hair and teeth. The ED1 gene responsible for the disorder undergoes extensive alternative splicing and to date few studies have concerned the full length transcript. We screened 52 unrelated families or sporadic cases for mutation in the full coding sequence of this gene. SSCA analysis or direct sequencing allowed identification of mutations in 34 families: one initiation defect, twenty-two missenses, two nonsense, eight insertions or deletions, and a large deletion encompassing all the ED1 gene. Fourteen of these mutations have not been previously described, including five missenses. One third of identified mutations were localised in codons 155 and 156, affecting CpG dinucleotides and nine of them correspond to the R156H missense. Hypothesis of a founder effect has been ruled out by haplotype analysis of flanking microsatellites. These recurrent mutations indicate the functional importance of the positively charged domain of the protein. Including our data, there are now 56 different mutations reported in 85 independent patients, that we have tabulated. Review of clinical features in the present series of affected males and female carriers showed no obvious correlation between the type of mutations, the phenotype and its severity. The X-chromosome pattern of inactivation in leucocytes showed little correlation with expressivity of the disease in female carriers. Finally this study is useful for functional studies of the protein and to define a diagnostic strategy for mutation screening of the ED1 gene.

show abstract

“…From this 27-locus marker set, on average 10.1 markers were informative within a given family (range 5-15 loci per family). Because these loci all map to a ∼20-cM region spanning the centromere (Nelson et al 1995;Weeks et al 1995), the average intermarker distance is ∼2 cM.…”

Section: Genetic Distance Across the Centromerementioning

confidence: 99%

“…Until recently, the lack of detailed long-range physical maps spanning centromeres (and uncertainty regarding the functional identification of a centromere itself) has precluded the definitive measurement of recombination rates at human centromeres. Preliminary comparisons of physical with genetic distances at or near the centromeres of several human chromosomes have resulted in various estimates of pericentromeric recombination rates, some consistent (Carson and Simpson 1991;Lichter et al 1993;Weeks et al 1995) and others inconsistent (Jabs et al 1991;Janson et al 1991; Van Hul et al. 1993) with a suppression of centromeric meiotic exchange.…”

mentioning

confidence: 99%

Physical and Genetic Mapping of the Human X Chromosome Centromere: Repression of Recombination

Mahtani¹,

Willard²

1998

Genome Res.

122

View full text Add to dashboard Cite

Classical genetic studies in Drosophila and yeast have shown that chromosome centromeres have a cis-acting ability to repress meiotic exchange in adjacent DNA. To determine whether a similar phenomenon exists at human centromeres, we measured the rate of meiotic recombination across the centromere of the human X chromosome. We have constructed a long-range physical map of centromeric ␣-satellite DNA (DXZ1) by pulsed-field gel analysis, as well as detailed meiotic maps of the pericentromeric region of the X chromosome in the CEPH family panel. By comparing these two maps, we determined that, in the proximal region of the X chromosome, a genetic distance of 0.57 cM exists between markers that span the centromere and are separated by at least the average 3600 kb physical distance mapped across the DXZ1 array. Therefore, the rate of meiotic exchange across the X chromosome centromere is <1 cM/6300 kb (and perhaps as low as 1 cM/17,000 kb on the basis of other physical mapping data), at least eightfold lower than the average rate of female recombination on the X chromosome and one of the lowest rates of exchange yet observed in the human genome.Meiotic exchange is not distributed randomly along the length of eukaryotic chromosomes; indeed, much regional variation in recombination frequency has been observed. Perhaps the most conspicuous departure from uniformity is the dramatic repression of exchange found near eukaryotic chromosome centromeres and some telomeres (Mather 1936(Mather , 1939. Repression of meiotic recombination adjacent to the centromere (the centromere effect) is most obvious on the Drosophila X chromosome in which the centric heterochromatin, comprising half of the chromosome's cytogenetic length, barely contributes to its genetic length (Mather 1939;Roberts 1965); a similar centromere-associated repression of recombination is found on the autosomes of Drosophila (Beadle 1932;Painter 1935;Thompson 1963). Some of this repression of exchange is caused by the large blocks of heterochromatin present at the centromeres of higher eukaryotes (Willard 1990;Murphy and Karpen 1995), because heterochromatin, at least in Drosophila, is a poor substrate for recombination regardless of chromosomal location (Baker 1958). Because deletions of centric heterochromatin result in lowered levels of meiotic exchange in centromere-adjacent euchromatin (Yamamoto and Miklos 1978), the presence alone of heterochromatin at Drosophila centromeres does not fully explain the centromere effect. Rather, the centromere seems to exert a suppression of recombination that spreads to adjacent DNA.Studies in yeast support a similar centromeric suppression of meiotic exchange in proximal chromosome regions, although this effect may be less pronounced. In both Saccharomyces cerevisiae and Schizosaccharomyces pombe, mitotic recombination is relatively more frequent than meiotic recombination in the proximity of centromeres (Malone et al. 1980;Minet et al. 1980). Direct evidence for the centromere effect in yeast has come from studies of c...

show abstract

A high-resolution genetic linkage map of the pericentromeric region of the human X chromosome

Cited by 12 publications

References 32 publications

An integrated genetic and physical map of the bovine X Chromosome

An integrated genetic and physical map of the bovine X Chromosome

Mutational spectrum of the ED1 gene in X-linked hypohidrotic ectodermal dysplasia

Physical and Genetic Mapping of the Human X Chromosome Centromere: Repression of Recombination

Contact Info

Product

Resources

About