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1.
Extremely complex repeat shuffling during germline mutation at human minisatellite B6.7 总被引:8,自引:0,他引:8
Human minisatellite B6.7 is a highly variable locus showing extensive heterozygosity with alleles ranging from six to >500 repeat units. Paternal and maternal mutation rates to new length alleles were estimated from pedigrees at 7.0 and 3.9% per gamete, respectively, indicating that B6.7 is one of the most unstable minisatellites isolated to date. Mutation at this locus was also analysed by small pool PCR of sperm and blood DNA. Male germline instability varied from <0.8 to 14% per allele and increased with tandem array size. In contrast, the frequency of mutants in somatic (blood) DNA was far lower (<0.5%), consistent with a meiotic origin of germline mutants. Sperm mutants were further characterized by minisatellite variant repeat mapping using four major polymorphic sites within the B6.7 repeats. This highly informative system revealed a wide variety of changes in allele structure, including simple intra-allelic duplications and deletions and more complicated inter- and intra-allelic transfers of repeat blocks, as seen at other human minisatellites. The main mode of sperm mutation, however, resulted in extremely complex allele reorganization with evidence of inter-allelic transfer plus the generation of novel repeats by rearrangement at the sub-repeat level, suggesting that recombinational instability at B6.7 is a complex multistep process. 相似文献
2.
Case-control studies have implicated rare length H-ras minisatellite alleles in cancer risk. In Europeans, this locus has four common alleles, and a larger number of rare alleles; possession of a rare allele has been identified as a risk factor responsible for 5-10% of some cancers. This unusual model of predisposition has been controversial in case-control studies, but also makes characteristic predictions about the population genetics of the locus, which we examine in this study. Using minisatellite variant repeat ("MVR") mapping, and compound haplotypes composed of the minisatellite and surrounding substitutional polymorphisms, we have reconstructed the main steps in the evolution of this locus in human populations. MVR-calibrated measurements of allele length yield rare allele frequencies significantly higher than most previous studies, and show that most other analyses have not distinguished two common alleles of 84 and 85 repeat units. Alleles classified as "rare" in European populations predominate (70%) in the African sample studied. Small-pool PCR (SP-PCR) analysis on common alleles in sperm DNA gives an estimate for the germline minisatellite mutation rate of about 0.05% (95% confidence upper limit 0.15%). Overall, our results do not reflect a locus subject to frequent mutation and strong selection, and are difficult to reconcile with the proposed cancer predisposition. Restricted variation at this locus is most simply explained by low mutation rate, and although definitive case-control studies can only be performed using methods capable of reproducibly distinguishing rare and common alleles, our work suggests that most studies to date have not resolved alleles adequately. 相似文献
3.
During recent years the HRAS1 minisatellite has been analysed by several authors because of its putative association with cancer susceptibility. The aim of this report is to test the usefulness of this minisatellite in investigating human population relationships. We have studied 370 chromosomes from two well-differentiated populations: Galicia (North-west Iberia) and South-east Africa, as well as available data on allele length gene frequencies. The fragment analysis results show a strong tendency to differentiate between non-African and African populations. In spite of the usefulness of fragment analysis, the minisatellite variant repeat (MVR) approach of the HRAS1 minisatellite appears to be a more powerful method for use in human population studies, due to the high level of diversity of its interspersion pattern structures. In addition, this approach has allowed us to define some new structural characteristics of this minisatellite. Four different major groups of human HRAS1 minisatellite alleles could be distinguished following a structural criterion based on the MVR code. Furthermore, the characterisation of the HRAS1 minisatellite in chimpanzees revealed clear differences when compared to humans, not only with respect to the allele size but also to the internal structure. 相似文献
4.
Buresi C; Desmarais E; Vigneron S; Lamarti H; Smaoui N; Cambien F; Roizes G 《Human molecular genetics》1996,5(1):61-68
The internal structure of different alleles of the minisatellite present at
the 3' end of the apolipoprotein B (ApoB) gene has been analysed by
different approaches including sequencing. The repeat unit arrangements of
the minisatellite on 570 chromosomes belonging to European and African
populations were thus determined. It was possible to group the alleles
using this structural criterion much more clearly than by the number of
repeat units which can in some cases be misleading in case-control genetic
epidemiological studies using such DNA sequences as markers. We were thus
able to define five types (a to e) of alleles and their subtypes and to
recognize clearly those which are, respectively, specific of the African
and Caucasian populations. A phylogeny of the different alleles found in
all human populations could also be deduced by this approach. The different
putative mutational events leading from one type, or subtype, to the other
were simply determined as point mutations, expansion/contraction and
conversion events. Sequencing of one chimpanzee's allele suggested that the
ApoB minisatellite was present before divergence between great apes and
humans. It was determined also that a particular ApoB gene haplotype was in
linkage disequilibrium with the minisatellite (a) type of alleles. This and
the observation that the potential scaffold attachment regions (SAR) and
topoisomerase II binding sites present in this minisatellite have a
different distribution between the Caucasian and the African specific
alleles suggest that the minisatellite could be involved in the
epidemiology of coronary diseases.
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5.
De novo mutations and allelic diversity at minisatellite locus D7S22 investigated by allele-specific four-state MVR-PCR analysis 总被引:2,自引:0,他引:2
We have studied the allelic diversity and de novo mutations at the
hypervariable minisatellite locus D7S22. A four-state minisatellite variant
repeat unit mapping by PCR (MVR-PCR) method was developed for this purpose,
and a substitution polymorphism close to the repeat array was used to
design allele-specific flanking primers to study individual haplotypes in
genomic DNA. A total of 150 alleles from different allele size groups and
flanking haplotypes were mapped. On average, MVR-codes extending 65 repeats
(2.4 kb) into the repeat array were obtained. The interspersion patterns of
variant repeats were highly polymorphic. However, subgroups of alleles
close in size and with identical flanking haplotype revealed common
MVR-code characteristics indicating a close evolutionary relationship.
Unlike the situation in many other hypervariable minisatellites, no
polarized variability was revealed at this minisatellite locus. Fifty four
small families with D7S22 de novo mutations were analysed by MVR-PCR. The
sites where the length change occurred were revealed in 22 cases, while in
32 cases the mutation obviously occurred further into the repeat array. In
agreement with a non-polar distribution of the allelic variation, there was
no evidence for a hypermutable hot spot for mutation within the repeat
array. Comparison of MVR-codes in the mutant and progenitor in gain
mutations indicated that at least one, possibly four cases, reflected
inter- allelic events. Together with evidence from DNA sequencing of
alleles of <2 kb, this indicates that as many as half of the gain
mutations might be inter-allelic events in D7S22. Based on these results,
different factors which might affect the mutation rate are discussed.
相似文献
6.
7.
Verbenko DA Pogoda TV Spitsyn VA Mikulich AI Bets LV Bebyakova NA Ivanov VP Abolmasov NN Pocheshkhova EA Balanovskaya EV Tarskaya LA Sorensen MV Limborska SA 《European journal of human genetics : EJHG》2003,11(6):444-451
Apolipoprotein B 3' (3' ApoB) minisatellite polymorphism was studied in healthy unrelated individuals from the Russian Federation and the Republic of Belarus, in 10 populations from five ethnic groups: Russians, Byelorussians, Adygeis, Kalmyks and Yakuts. The analysis was carried out using PCR and electrophoresis followed by silver staining. Overall, 25 alleles of the 3' ApoB minisatellite, ranging from 25 to 55 repeats, were detected. Heterozygosity indices were high and varied from 0.73 to 0.84. The distributions of alleles of this minisatellite in the Caucasoid populations (Russians, Byelorussians and Adygeis) had a bimodal character, whereas that for Mongoloid populations (Kalmyks and Yakuts) had a unimodal distribution. Nei's genetic distances between the populations studied and some reference populations of Europe and Asia were estimated. Despite their allele distribution homogeneity, different East Slavonic ethnic groups were clearly resolved by multidimensional analyses. The East Slavonic and Adygei populations revealed a high similarity with European Caucasoids. The Mongoloid populations (Kalmyks and Yakuts) were considerably different from those of the European Caucasoid populations, but were similar to other Asian Mongoloid populations. The results demonstrate the variability of 3' ApoB minisatellite polymorphism not only in distant populations but also, to a certain extent, in genetically relative ones. 相似文献
8.
The molecular determination of HLA-Cw alleles in the Mandenka (West Africa) reveals a close genetic relationship between Africans and Europeans 总被引:4,自引:0,他引:4
HLA-Cw alleles were determined by high-resolution polymerase chain reaction-sequence-specific oligonucleotide probe (PCR-SSOP) oligotyping in a sample of 165 Mandenka, a population from Eastern Senegal previously analysed for A/B and DRB/DQB polymorphisms. A total of 18 Cw alleles were identified, with Cw*0401/5 and 1601 accounting for a combined frequency of 36%. A comparison of Cw allele frequencies among several populations of different origins, Mandenka, Swiss, English, Ashkenazi Jews from the UK and Japanese, reveals a high genetic heterogeneity among them, but also a much closer relationship between Mandenka, Europeans and Ashkenazi than between any of these populations and Japanese. Cw*0501, Cw*0701 and Cw*1601, among others, appear to be restricted to the European and African populations. Many B-Cw haplotypes exhibit a significant linkage disequilibrium in the Mandenka, among which B*3501-Cw*0401 and B*7801-Cw*1601, formed by the most frequent B and Cw alleles, and B*5201-Cw*1601, B*5702-Cw*18 and B*4410-Cw*0401, not yet observed in other populations. B*3501-Cw*0401 is found with similar frequencies in Europeans. The results possibly support a close historical relationship between Africans and Europeans as compared to East Asiatics. However, the HLA-Cw frequency distributions are characterised by an excess of heterozygotes, indicating that balancing selection may have played a role in the evolution of this polymorphism. 相似文献
9.
Nucleotide sequence analysis of the apolipoprotein B 3' VNTR 总被引:3,自引:2,他引:1
Variable number of tandem repeat (VNTR) loci typically exhibithigh rates of germline mutations that alter allele length andthus are ideal models for examining processes governing repeatsequence instability. We have characterized by nucleotide sequencingthe internal structure of the apolipoprotein B (Apo B) 3' VNTRin a sample of same- and different-sized alleles previouslyassociated with flanking marker haplotypes. Significant linkagedisequilibrium between flanking polymorphisms and minisatellitealleles excludes unequal recombinatlon as the predominant mechanismof mutation at the Apo B VNTR and is consistent with intra-allelicmutational processes such as replication slippage and/or unequalsister chromatid exchange. Diversity among different lengthalleles was distinctly polar and was usually atiributable tochanges in copy number at one particular repeat sequence. Analysisof predicted secondary structures for the dimeric repeats demonstrateda relationship between variability and the potential to formself-complementary intermediates. Preferential instability ofthe variable repeat: (i) was a function of its location withinthe tandem array; (ii) was not solely dependent on copy number;and (iii) may be related to the base composition of the VNTRand the degree of self-complementarity between the dimeric repeatsequences. The data suggest that polarized variability may beindependent of the mutational process(es) generating lengthvariation at minisatellite loci and suggest a possible alternativemechanism of mutation that involves the formation of secondarystructures. 相似文献
10.
The insulin minisatellite or variable number of tandem repeats locus (INS VNTR) is the best candidate for the type 1 diabetes mellitus (T1DM) susceptibility locus IDDM2. Small class I alleles associate with predisposition to T1DM, whereas large class III alleles associate with dominant protection. We have analysed variant repeat distribution within the minisatellite and combined this with flanking haplotypes to define five new ancestral allele lineages. Class III alleles divide into two highly diverged lineages, IIIA and IIIB, which correspond perfectly to the previously defined Protective (PH) and Very Protective (VPH) haplotypes, respectively. Class I alleles are divided into three newly defined lineages, IC+, ID+ and ID-, by a combination of variant repeat distributions and flanking haplotypes. All class I alleles are equally predisposing to T1DM except for ID- alleles which are protective when transmitted from ID-/III heterozygous fathers. Similar results have been previously reported for alleles of 42 repeats in length (allele 814) which represent a subset of the ID- lineage. Division of class ID- alleles into those of 42 repeats and those of other sizes suggested that this protective effect was a feature of all ID- alleles, irrespective of size. ID- alleles are only clearly distinguished from all other alleles by an MSPI(-) variant within IGF2 downstream of the minisatellite, suggesting that the apparent role of the minisatellite in susceptibility to T1DM may be modified by neighbouring haplotype and therefore that IDDM2 could have a multi-locus aetiology. 相似文献
11.
HLA polymorphism in Bulgarians defined by high-resolution typing methods in comparison with other populations 总被引:7,自引:0,他引:7
Ivanova M Rozemuller E Tyufekchiev N Michailova A Tilanus M Naumova E 《Tissue antigens》2002,60(6):496-504
In the present study we analyzed for the first time HLA class I and class II polymorphisms defined by high-resolution typing methods in the Bulgarian population. Comparisons with other populations of common historical background were performed. Most HLA-A, -B, -DRB alleles and haplotypes observed in the Bulgarian population are also common in Europe. Alleles and haplotypes considered as Mediterranean are relatively frequent in the Bulgarian population. Observation of Oriental alleles confirms the contribution of Asians to the genetic diversity of Bulgarians. The use of high-resolution typing methods allowed to identify allele variants rare for Europeans that were correlated to specific population groups. Phylogenetic and correspondence analyses showed that Bulgarians are more closely related to Macedonians, Greeks, and Romanians than to other European populations and Middle Eastern people living near the Mediterranean. The HLA-A,-B,-DRB1 allele and haplotype diversity defined by high-resolution DNA methods confirm that the Bulgarian population is characterized by features of southern European anthropological type with some influence of additional ethnic groups. Implementation of high-resolution typing methods allows a significantly wider spectrum of HLA variation to be detected, including rare alleles and haplotypes, and further clarifies the origin of Bulgarians. 相似文献
12.
P. Chiurazzi G. Destro-Bisol M. Genuardi B. A. Oostra G. Spedini G. Neri 《American journal of medical genetics. Part A》1996,64(1):216-219
We report on the allele distributions in a normal black African population at two microsatellite loci neighbouring the FRAXA locus and at the CGG repeat in the 5′ end of the FMR-1 gene, which causes the fragile X syndrome. The CGG repeat distribution was found to be similar to that of other ethnic groups, as well as to that of other nonhuman primates, possibly predicting a comparable prevalence of fragile X in Africa. Significant linkage disequilibrium has been observed between fragile X mutations and alleles of the DXS548 and FRAXAC1 loci in European and Asian populations, and some founder chromosomes may be extremely old. Those associated with FRAXAC1-A and DXS548-2 alleles are not present in the Asian fragile X samples. We searched for these alleles and their frequency in the well defined Bamileke population of Cameroon. All previously described alleles and some new ones were found in this sample, supporting the hypothesis of their pre-existence and subsequent loss in Asian populations. Finally, the heterozygosity of the Bamileke sample was significantly higher at both marker loci and comparable to that of Europeans at the CGG repeat, confirming the notion that genetic diversity is greater in Africans than in other groups and supporting the view that evolution of modern man started in Africa. © 1996 Wiley-Liss, Inc. 相似文献
13.
X-L. HUANG K. TAMAKI T. YAMAMOTO K. SUZUKI H. NOZAWA R. UCHIHI Y. KATSUMATA D. L. NEIL 《Annals of human genetics》1996,60(4):271-279
To sample the diversity of allelic structures at the D7S21 (MS31A) locus in the Japanese, allele-specific minisatellite variant repeat mapping using polymerase chain reaction (MVR-PCR) was performed on genomic DNA from a number of Japanese individuals. Three polymorphic positions in the MS31A 5' flanking DNA were typed from 214 un-related Japanese, and the distribution of haplotypes was analysed. Allele-specific MVR-PCR, using primers that discriminate between different alleles at these polymorphic positions in heterozygous individuals, allows single alleles to be mapped from genomic DNA in approximately 80% of Japanese. 149 Japanese alleles have been mapped to date and all of them, except for two pairs of indistinguishable alleles, have different internal structures. More than half of the mapped alleles showed similar regions of internal structure to other alleles and were classified into groups on this basis. 相似文献
14.
The FCGR3B gene codes for the FcgammaR3b receptor, which occurs in three polymorphic forms representing the human neutrophil antigens (HNA)-1a, HNA-1b, and HNA-1c. The alleles that code for these antigens are FCGR3B*1, FCGR3B*2, and FCGR3B*3, respectively. New variants of these alleles have been recently described. In order to study the frequency of these alleles and the occurrence of variant forms, we sequenced part of the FCGR3B gene in 149 individuals belonging to four distinct Brazilian populations, i.e., 60 Amerindians, 30 Whites of European descent, 30 Afro-Brazilians, and 30 Japanese. The FCGR3B*1 allele showed high frequency among Amerindians (0.850), with the value detected representing the highest frequency described thus far for this allele in population studies. Its frequency was 0.660 in the Japanese population studied, a value equal to that observed in Afro-Brazilians (0.600) and higher than that observed in Whites (0.480). The FCGR3B*3 allele was only found among Afro-Brazilians, where it occurred at a frequency of 0.080, which was lower than the frequency observed among Afro-North Americans (0.207) and Ugandans (0.166). Two variant haplotypes were detected among Amerindians and Afro-Brazilians, occurring in six individuals (four Amerindians and two Afro-Brazilians). The variant haplotype FCGR3B*1 A227G, which occurred in homozygosis in two Amerindians and in heterozygosis in two Afro-Brazilians, is described for the first time in the present report. In general, these data reveal variability in the frequency of alleles of the FCGR3B gene compared to other populations of the same genetic background in other regions of the world. 相似文献
15.
MS205 Minisatellite Diversity in Basques: Evidence for a Pre-Neolithic Component 总被引:2,自引:0,他引:2
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A number of studies have suggested that Basques might be a relic of Mesolithic Europeans who escaped much of the homogenization brought about by the Neolithic expansion. In an attempt to add new insights into this hypothesis, MS205 minisatellite diversity has been investigated by Minisatellite Variant Repeat (MVR) analysis in a sample of >100 autochthonous individuals from the Basque Country, along with 24 Castilian (N. Spain) and 23 individuals from the United Kingdom. These populations were examined in the context of the available world database for MS205 alleles. To deduce the similarities among populations, we have applied a phylogenetic approach that takes into account similarity between alleles. The variability of these populations seems to be a subset of the greater and presumably older African diversity, as has been suggested previously for non-Africans. Within non-Africans, Basques seem to cluster with other Northern European populations; however, some apparently Basque-specific alleles can be dated back to post-Aurignacian times, supporting the continuity of some lineages of this population since the Upper Paleolithic period. 相似文献
16.
Mutation rate heterogeneity and the generation of allele diversity at the human minisatellite MS205 (D16S309) 总被引:10,自引:2,他引:10
Many tandemly repeated minisatellite loci display extreme levels of length
variation as a consequence of high rates of spontaneous germline mutation
altering repeat copy number. Direct screening for new allele lengths by
small-pool PCR has shown that instability at the human minisatellite locus
MS205 (D16S309) is largely germline specific and usually results in the
gain or loss of just a few repeat units. Structural analysis of the order
of variant repeats has shown that these events occur preferentially at one
end of the tandem array and can result in complex rearrangements including
the inter-allelic transfer of repeat units. In contrast, putative mutants
recovered from somatic DNA occur at a substantially lower rate and are
simple and non- polar in nature. Germline mutation rates vary considerably
between alleles, consistent with regulation occurring in cis. Although
examination of DNA sequence polymorphisms immediately flanking the
minisatellite reveals no definitive associations with germline mutation
rate variation, differences in rate may be paralleled by changes in
mutation spectrum. These findings help to explain the diversity of MS205
allele structures in modern humans and suggest a common mutation pathway
with some other minisatellites.
相似文献
17.
Previous analysis of germline mutation at highly unstable GC-rich minisatellites with continuous allele size distributions revealed similar meiotic recombinational mechanisms operating at all loci investigated. The insulin minisatellite has been studied intensively due to its associations with diabetes, polycystic ovary syndrome, obesity and birth size. Its bimodal allele size distribution in Caucasians suggests a much lower mutation rate and possible differences in the mutation process compared with highly unstable minisatellites. Mutation at the insulin minisatellite therefore was studied both indirectly from allele diversity surveys and directly by recovering de novo mutants from sperm DNA. Structural analysis of variant repeat distributions in 876 alleles identified 189 different alleles, almost all of which could be assigned to one of three very distinct lineages. Variation within a lineage was minor and due mainly to the gain or loss of one or a few repeat units. These events most probably arise by mitotic replication slippage at a frequency of perhaps 10(-3)per gamete. Sperm DNA analysis revealed a second class of mutation occurring at a frequency of approximately 2 x 10(-5)that involved highly complex intra- and inter-allelic rearrangements very similar to those seen at unstable minisatellites. These complex rearrangements were not seen in somatic DNA and are probably meiotic in origin. Minisatellite homozygosity did not reduce the frequency of these mutants in sperm. The insulin minisatellite therefore appears to evolve by two distinct processes: one involving slippage-like events and the second resulting in complex recombinational turnover of allele structure. 相似文献
18.
Andrey Khrunin Dmitry Verbenko Kseniya Nikitina Svetlana Limborska 《American journal of human biology》2007,19(6):741-750
The Komi (Komi-Zyryan) people are one of the most numerous ethnic groups belonging to the Finno-Ugric linguistic community. They occupy an extensive territory in north Russia to the west of the Ural Mountains, in the northeast of the East European Plain. This is an area of long-term interactions between Europeans and North Asians. Genetic variability was evaluated in two geographically distinct populations, the Izhemski and Priluzski Komi. We searched for polymorphisms of the TP53 gene (a 16-bp duplication in intron 3 and three RFLPs: for Bsh1236I at codon 72, for MspI in intron 6, and for BamHI in the 3' flanking region) and for variable number tandem repeat (VNTR) polymorphisms of locus D1S80 and of the 3' untranslated region of the gene for apolipoprotein B (ApoB). Some data from our previous studies of TP53, 3'ApoB, and D1S80 variability were involved in the comparison of Komi with other Eastern European populations. Multidimensional scaling analysis of genetic distances was used for the evaluation of genetic relationships between populations. The results revealed some affinity between Priluzski Komi and Eastern Slavonic populations, and significant segregation of Izhemski Komi from other ethnic groups studied. The unique genetic features of Izhemski Komi may have been determined by their ethnogenesis or the pressure of environmental factors, such as special nutrition and adaptation to extreme climatic conditions. 相似文献
19.
Human leucocyte antigen-A, -B, -Cw, -DRB1, -DQA1 and -DQB1 polymorphisms were examined in the Azorean population. The data were obtained at high-resolution level, using polymerase chain reaction (PCR) with sequence-specific primer, PCR-sequence-specific oligonucleotides and sequence-based typing. The most frequent allele in each locus was: A*0201 (24.5%), B*510101 (9.8%), Cw*0401 (14.8%), DRB1*070101 (18.3%), DQA1*0201 (17.4%) and DQB1*0301 (19.4%). The predominant extended haplotype was A*0202-B*1503-Cw*0202-DRB1*090102-DQA1*0303- DQB1*0202 (1.9%), which was found to be absent in the Portuguese mainland. The present study corroborates historical sources that say the Azores were populated not only by Portuguese but also by other Europeans, mostly Flemish people. Despite dendrogram analysis showing some remote Asian genetic affinities, the lack of specific alleles and haplotypes from those populations does not allow us to conclude for direct influence. Haplotype and allele frequencies in Azores show no homogeneous distribution between Oriental and Central islands of this archipelago. The Oriental islands harbour several haplotypes already found in mainland Portugal and identified as Mediterranean and European. The Central group of islands on the contrary clearly shows an influence of north Europeans (most probably derived from a well-documented Flemish settlement), with much less affinity to mainland Portugal. 相似文献
20.
R P Grewal G Cancel E P Leeflang A Dürr M S McPeek D Draghinas X Yao G Stevanin M O Alnot A Brice N Arnheim 《Human molecular genetics》1999,8(9):1779-1784
Segregation distortion has been reported to occur in a number of the trinucleotide repeat disorders. On the basis of a sperm typing study performed in patients of Japanese descent with Machado-Joseph disease (MJD), it was reported that disease alleles are preferentially transmitted during meiosis. We performed a sperm typing study of five MJD patients of French descent and analysis of the pooled data shows a ratio of mutant to normal alleles of 379:436 (46.5:53.5%), which does not support meiotic segregation distortion. To confirm these results, sperm typing analysis was also performed using a polymorphic marker, D14S1050, closely linked to the MJD1 gene. Among 910 sperm analyzed, the allele linked to the disease chromosome was detected in 50.3% of the samples and the allele linked to the normal chromosome was found in 49.6% of the sperm. The difference in frequency of these two alleles is not significant ( P = 0.8423). Likelihood-based analysis of segregation distortion in the single sperm data using the SPERMSEG program also showed no support for segregation distortion at the gamete level in this patient population. The previous report on the Japanese patients also suggested that disease allele stability may be influenced by a trans effect of an intragenic polymorphism (987 G/C) in the wild-type allele. All of the French patients were heterozygous for this polymorphism. However, analysis of the variance in repeat number in sperm from the French MJD patients overlapped significantly with the variance in repeat number observed in the C/C homozygous Japanese patients. 相似文献