Sex Chromosome Nondisjunction Research Articles

Molecular studies on parental origin and cell stage of nondisjunction in sex chromosome aneuploidies

To study the parental origin and cell stage of nondisjunction in sex chromosome aneuploidies. Retrospectiving and analyzing the results of 385 cases of SCA confirmed by QF-PCR and karyotype analysis in the prenatal diagnosis center of Guangzhou Women and Children Medical Center from January 2015 to December 2020. The types of samples and prenatal diagnosis indications were analyzed. The parental origin and cell stage of nondisjunction in sex chromosome aneuploidies analyzed by comparing the short tandem repeat (STR) peak patterns of samples from fetuses and maternal peripheral blood. The results show that (1) There were 324 cases of nonmosaic SCA, 113 cases (113/324, 34.9%) were 45, XO, 118 cases (118/324, 36.4%) were 47, XXY, 48 cases (48/324, 14.8%) were 47, XXX and 45 cases (45/324, 13.9%) were 47, XYY. 68 (45/324, 60.2%) cases of 45, X were detected in villus samples. The other SCA cases were mainly detected in amniotic fluid samples. There were 61 mosaic SCA samples, 58(58/61, 95.1%) of mosaic SCA samples were mosaic 45, X. (2) The top two indications of 45, X cases are increased nuchal translucency(53/113, 46.9%) and fetal cystic hygroma (41/113, 36.3%), while the most common indication of other types of SCA was high risk of NIPT(170/272, 62.5%). (3) Among 45, X cases, there were 88 cases (88/113, 77.9%) inherit their single X chromosome from their mother and 25 cases (25/119, 22.1%) from their father. In 47, XXY samples, 47 cases (47/118, 39.8%) of chromosome nondisjunction occurred in meiosis stage Ⅰ of oocytes, 51 cases (51/118, 43.2%) occurred in meiosis stage Ⅰ of spermatocytes, and 20 cases (20/118, 16.9%) occurred in meiosis stage Ⅱ of oocytes. Among 47, XXX samples, 29 cases (29/48, 60.4%) of X chromosome nondisjunction occurred in meiosis stage Ⅰof oocytes, 15 cases (15/48, 31.3%) occurred in meiosis stage Ⅱ of oocytes, and 4 cases (4/48, 8.3%) occurred in meiosis stage Ⅱ of spermatocytes. In summary, the cases of 45, X were mainly diagnosed by villous samples for abnormal ultrasound findings. The other cases of SCA were mainly diagnosed by amniocentesis samples for abnormal NIPT results. Different types of SCA, the origin and occurrence period of sex chromosome nondisjunction were different.

Mycotoxin T-2 of Fusarium tricinctum and chromosome changes in Chinese hamster bone marrow.

HereditasVolume 93, Issue 2 p. 329-332 Open Access Mycotoxin T-2 of Fusarium tricinctum and chromosome changes in Chinese hamster bone marrow HANNU NORPPA, HANNU NORPPA Institute of Occupational Health, Helsinki, FinlandSearch for more papers by this authorMERJA PENTTILÄ, MERJA PENTTILÄ Institute of Occupational Health, Helsinki, FinlandSearch for more papers by this authorMARJA SORSA, Corresponding Author MARJA SORSA Institute of Occupational Health, Helsinki, FinlandInstitute of Occupational Health, Haartmaninkatu I, SF-00290 Helsinki 29, FinlandSearch for more papers by this authorEEVA-LIISA HINTIKKA, EEVA-LIISA HINTIKKA College of Veterinary Medicine, Helsinki, FinlandSearch for more papers by this authorTAINA ILUS, TAINA ILUS Technical Research Centre of Finland, Helsinki, FinlandSearch for more papers by this author HANNU NORPPA, HANNU NORPPA Institute of Occupational Health, Helsinki, FinlandSearch for more papers by this authorMERJA PENTTILÄ, MERJA PENTTILÄ Institute of Occupational Health, Helsinki, FinlandSearch for more papers by this authorMARJA SORSA, Corresponding Author MARJA SORSA Institute of Occupational Health, Helsinki, FinlandInstitute of Occupational Health, Haartmaninkatu I, SF-00290 Helsinki 29, FinlandSearch for more papers by this authorEEVA-LIISA HINTIKKA, EEVA-LIISA HINTIKKA College of Veterinary Medicine, Helsinki, FinlandSearch for more papers by this authorTAINA ILUS, TAINA ILUS Technical Research Centre of Finland, Helsinki, FinlandSearch for more papers by this author First published: December 1980 https://doi.org/10.1111/j.1601-5223.1980.tb01372.xAboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume93, Issue2December 1980Pages 329-332 ReferencesRelatedInformation

The meiotic behaviour of B-chromosomes and their effect on thesegregation of sex chromosomes in males of Hemerobius marginatus L. (Hemerobidae, Neuroptera)

A sample of 62 Hemerobius marginatus males was studied, and ten individuals were found to carry one or two B-chromosomes, which were isopycnotic in meiosis. At pachytene, univalent B-chromosomes or a B-chromosome bivalent showed association with the heteropycnotic sex chromosome pair. No such association was found at diakinesis. At metaphase I, syntelically orientated univalent B-chromosomes showed preferential segregation from each other. The presence of univalent B-chromosomes-either one or two-was found to increase sex chromosome nondisjunction significantly. Among sex chromosome nondisjunctionals, a B-chromosome was found to segregate preferentially from sex chromosomes, indicating preferential segregation of nonhomologous chromosomes. Both preferential segregation of univalent B-chromosomes from each other and a B-chromosome from sex chromosomes are explained by the model according to which pachytene association of chromosomes is able to determine segregation even in those cases where chromosomes are physically unlinked at meiotic prophase.

The nonsignificance of distance pairing for the regular segregation of the sex chromosomes in Hemerobius marginatus male. (Hemerobidae, Neuroptera)

Pachytene nuclei in Hemerobius marginatus male showed five autosomal bivalents and loosely paired X and Y chromosomes. In part of the cells, the paired condition was retained until late prometaphase. In these cells, the segregation of sex chromosomes was determined by the bivalent condition. In another part of the cells, sex chromosomes appeared as spatially well separated univalents at diakinesis, followed by their congression separately to the equator at the beginning of prometaphase, after which they were pulled near the poles by spindle fibers during the stabilization process of metaphase structure. On the basis of the behaviour of univalent sex chromosoms during prometaphase, it was concluded that no pairing occurring late at prometaphase was involved in the determination of their segregation. During metaphase I, the X and Y chromosomes did not reorientate, but showed stabilized positions near opposite poles, i.e., distance pairing. Nondisjunction of sex chromosomes occurred in only 0.6% of metaphase I cells. The determination of the segregation of univalent sex chromosomes was explained by the model according to which nonrandom desynapsis movement of chromosomes is responsible for their initial orientation to opposite spindle poles at the beginning of prometaphase.

Hyperthermia of male Drosophila melanogaster meiocytes induces abnormalities in both paternal and maternal sex chromosome sets of the offspring

Nondisjunction and loss of sex chromosomes caused by exposure of male Drosophila melanogaster to heat shock (HS) (37 degrees C for 1 h) has been studied to determine the role of mutation l(1)ts403 (sbr10) in the control of chromosome segregation during cell division. Hyperthermia of males at the pupal stage has been demonstrated to increase the number of offspring with abnormalities of not only paternal, but also maternal sex chromosome sets. According to the criterion used, there is a temperature-sensitive period of spermatogenesis, which presumably coincides with meiosis. Phenotypes of some individuals correspond to the presence of two sex chromosomes of obtained from the same parent. The frequency of abnormal chromosome sets in the offspring of male carriers of the sbr10 mutation is about two times higher than in the offspring of males without this mutation.

Etoposide exposure during male mouse pachytene has complex effects on crossing-over and causes nondisjunction

In experiments involving different germ-cell stages, we had previously found meiotic prophase of the male mouse to be vulnerable to the induction of several types of genetic damage by the topoisomerase-II inhibitor etoposide. The present study of etoposide effects involved two end points of meiotic events known to occur in primary spermatocytes—chromosomal crossing-over and segregation. By following assortment of 13 microsatellite markers in two chromosomes (Ch 7 and Ch 15) it was shown that etoposide significantly affected crossing-over, but did not do so in a uniform fashion. Treatment generally changed the pattern for each chromosome, leading to local decreases in recombination, a distal shift in locations of crossing-over, and an overall decrease in double crossovers; at least some of these results might be interpreted as evidence for increased interference. Two methods were used to explore etoposide effects on chromosome segregation: a genetic experiment capable of detecting sex-chromosome nondisjunction in living progeny; and the use of FISH (fluorescence in situ hybridization) technology to score numbers of Chromosomes X, Y, and 8 in spermatozoa. Taken together these two approaches indicated that etoposide exposure of pachytene spermatocytes induces malsegregation, and that the findings of the genetic experiment probably yielded a marked underestimate of nondisjunction. As indicated by certain segregants, at least part of the etoposide effect could be due to disrupted pairing of achiasmatic homologs, followed by precocious sister-centromere separation. It has been shown for several organisms that absent or reduced levels of recombination, as well as suboptimally positioned recombination events, may be associated with abnormal segregation. Etoposide is the only chemical tested to date for which living progeny indicates an effect on both male meiotic crossing-over and chromosome segregation. Whether, however, etoposide-induced changes in recombination patterns are direct causes of the observed malsegregation requires additional investigation.

Effects of male age on the frequencies of germinal and heritable chromosomal abnormalities in humans and rodents

Objective To review evidence regarding the effects of male age on germinal and heritable chromosomal abnormalities using available human and rodent studies and to evaluate possible underlying mechanisms. Design Review of English language-published research using MEDLINE database, excluding case reports and anecdotal data. Result(s) There was little evidence from offspring or germ cell studies for a generalized male age effect on autosomal aneuploidy, except in rodents. Sex chromosomal nondisjunction increased with age in both human and rodent male germ cells. Both human and rodent data showed age-related increases in the number of sperm with chromosomal breaks and fragments and suggest that postmeiotic cells are particularly vulnerable to the effects of aging. Translocation frequencies increased with age in murine spermatocytes, at rates comparable to mouse and human somatic cells. Age-related mechanisms of induction may include accumulation of environmental damage, reduced efficiency of DNA repair, increased genomic instability, genetic factors, hormonal influences, suppressed apoptosis, or decreased effectiveness of antioxidants and micronutrients. Conclusion(s) The weight of evidence suggests that the increasing trend toward fathering at older ages may have significant effects on the viability and genetic health of human pregnancies and offspring, primarily as a result of structural chromosomal aberrations in sperm.

Genes and male infertility: what can go wrong?

Genes and male infertility: what can go wrong?

Sperm-FISH analysis and human monitoring: a study on workers occupationally exposed to styrene

Occupational exposure to styrene, a chemical extensively used worldwide, is under investigation for possible detrimental effects on human health, including male reproductive capacity. Aneuploidy in germ cells is the main cause of infertility, abortions and congenital diseases. Fluorescence in situ hybridisation (FISH), is the most efficient cytogenetic molecular technique to date to analyse numerical alterations of chromosomes in spermatozoa. We investigated the frequencies of aneuploidy and diploidy in individuals occupationally exposed to styrene and in healthy unexposed controls. We performed multicolour FISH, using DNA probes specific for the centromeric regions of sex chromosomes and chromosome 2, in decondensed sperm nuclei of samples with normal semen parameters for a total of 18 styrene-exposed subjects and 13 unexposed controls of the same age range. Exposed individuals had worked for at least 2 years during the last 5 years, and continuously for 6 months, in factories producing reinforced plastics. The incidence of aneuploidy and diploidy for the tested chromosomes did not show a statistically significant difference between workers and controls. The exposure to styrene was associated with increased frequencies of nullisomy for sex chromosomes in the group of non-smokers, although only a limited number of subjects belonged to this sub-group. Considering the whole study population, age was associated with an increased frequency of XX disomy, whereas smoking was associated with meiosis II non-disjunction of sex chromosomes. Overall, confounding factors appeared to exert a more important effect than exposure to styrene on numerical chromosome alterations in sperm nuclei of subjects selected for normal semen parameters.

Exposure to acrylonitrile induced DNA strand breakage and sex chromosome aneuploidy in human spermatozoa

To explore acrylonitrile (ACN)-induced DNA strand breakage and sex chromosome aneuploidy in human spermatozoa, semen parameters were examined among 30 acrylonitrile-exposed workers according to WHO laboratory manual for the examination of human sperm. DNA strand breakage of sperm cells was investigated among 30 ACN-exposed workers using single cell gel electrophoresis (SCGE). The frequency of sex chromosome aneuploidy in sperm cells was analyzed among nine ACN-exposed workers using fluorescence in situ hybridization (FISH). The geometrical mean of sperm density was 75×10 6 ml −1 in exposure group, significantly lower than 140×10 6 ml −1 in the control. The geometrical mean of sperm number per ejaculum was 205×10 6 in exposure group, significantly lower than 280×10 6 in the control. The rates of comet sperm nuclei were 28.7% in exposure group, significantly higher than 15.0% in the control. Mean tail length was 9.8 μm in exposure group, longer than 4.3 μm in the control. The frequency of sex chromosome disomy was 0.69% in exposure group, significantly higher than 0.35% in the control. XY-bearing sperm was the most common sex chromosome disomy, with an average rate of 0.37% in exposure group, and 0.20% in the control. XX- and YY-bearing sperm accounted for an additional 0.09 and 0.23% in exposure group, and 0.05 and 0.10% in the control. The results indicate that ACN affect semen quality among ACN-exposed workers. ACN or its metabolites could induce reproductive defects as an in vivo multipotent genotoxic agent by inducing DNA strand breakage and sex chromosome non-disjunction in spermatogenesis.

The proximate determinants of sex ratio in C. elegans populations.

The soil nematode Caenorhabditis elegans is an example of a species in which self-fertilizing hermaphrodites predominate, but functional males continue to persist--allowing outcrossing to persevere at low levels. Hermaphrodites can produce male progeny as a consequence of sex chromosome non-disjunction or via outcrossing with males. Consequently, the genetics of sex determination coupled with the efficiency by which males find, inseminate and obtain fertilizations with hermaphrodites will influence the frequency at which males and outcrossing occurs in such populations. Behavioural and physiological traits with a heritable basis, as well as ecological characters, may influence male reproductive success and therefore sex ratio. Because sex ratio is tied to male reproductive success, sex ratio greatly affects outcrossing rates, patterns of genetic variation, and the ability of natural selection to act within populations. In this paper we explore the determinants of male frequency in C. elegans with a mathematical model and experimental data. We address the role of the genetic machinery of sex determination via sex chromosome non-disjunction on sex ratio and the influence of physiological components of C. elegans' life history that contribute to variation in sex ratio by way of male reproductive success. Finally, we discuss the short-term and long-term factors that are likely to affect sex ratio and breeding system evolution in species like C. elegans.

Semidominant Effect of the l(1)ts403 ( sbr 10 ) Mutation on Sex Chromosome Nondsjunction in Meiosis in Drosophila melanogaster Females Exposed to Heat

The sbrgene of Drosophila melanogasterbelongs to the NXF(nuclear export factor) family responsible for the mRNA transport from nucleus to cytoplasm. We have shown that in the heat-exposed (37°C, 1 h) females, the l(1)ts403(sbr10) mutation leads, in particular, to the high-frequency nondisjunction and loss of sex chromosomes in meiosis. For this trait, the incomplete dominance of the sbr10 mutation is observed. At the same time, the sbr10 mutation is recessive for many other traits of the heat-exposed flies: reduced viability, low fertility, impaired synthesis of the heat shock proteins, etc. The females heterozygous for the null allele (Df(1)vL4, a deletion eliminating gene srb) do not differ from females homozygous for the wild-type allele in frequency of the heat shock-induced nondisjunction and loss of sex chromosomes in meiosis. Because of this, the sbr10 mutation can be assigned to the gain-of-function alleles (those gaining the dominance function). Expression of the mutant sbr10 allele against the background of the wild-type allele suggests that in the heat shock-exposed females, the heat-modified product of this ts allele has an active effect on sex chromosome disjunction in meiosis.

Why Are There Males in the Hermaphroditic Species Caenorhabditis elegans?

The free-living nematode worm Caenorhabditis elegans reproduces primarily as a self-fertilizing hermaphrodite, yet males are maintained in wild-type populations at low frequency. To determine the role of males in C. elegans, we develop a mathematical model for the genetic system of hermaphrodites that can either self-fertilize or be fertilized by males and we perform laboratory observations and experiments on both C. elegans and a related dioecious species C. remanei. We show that the mating efficiency of C. elegans is poor compared to a dioecious species and that C. elegans males are more attracted to C. remanei females than they are to their conspecific hermaphrodites. We postulate that a genetic mutation occurred during the evolution of C. elegans hermaphrodites, resulting in the loss of an attracting sex pheromone present in the ancestor of both C. elegans and C. remanei. Our findings suggest that males are maintained in C. elegans because of the particular genetic system inherited from its dioecious ancestor and because of nonadaptive spontaneous nondisjunction of sex chromosomes, which occurs during meiosis in the hermaphrodite. A theoretical argument shows that the low frequency of male mating observed in C. elegans can support male-specific genes against mutational degeneration. This results in the continuing presence of functional males in a 99.9% hermaphroditic species in which outcrossing is disadvantageous to hermaphrodites.

The sbr gene product in Drosophila melanogaster and its orthologs in yeast (Mex67p) and human (TAP)

A DNA sequence from the 9F region of Drosophila melanogaster polytene chromosomes was cloned. Sequencing the cloned region and its comparison with the known sequences of the D. melanogaster genome showed that the cloned DNA part contains gene sbr and adjacent sequences. The literature data on the structure and functions of genes TAP in humans and Mex67 in yeast are discussed. These genes are orthologous to the sbr gene of Drosophila and control mRNA export from the nucleus to the cytoplasm. The literature evidence is consistent with the recessive expression of mutation l(1)ts403 (sbr10) upon heat treatment that is manifested as impaired HSP synthesis at the posttranscriptional level. However, it fails to explain the semidominant effect of the mutation manifested in high frequency of meiotic sex-chromosome nondisjunction in heat-treated females. A comparison of amino-acid sequences corresponding to the products of the three orthologous genes, TAP, Mex67, and sbr, showed that the sbr gene product of Drosophila is more similar to the human TAP factor than to the Mex67 factor in yeast.

Is there an interchromosomal effect in reciprocal translocation carriers? Sperm FISH studies.

Chromosome translocations have been known to affect disjunction of chromosomes unrelated to the translocation in the mouse and in Drosophila. However, in humans, an interchromosomal effect in chromosome translocations has not been demonstrated. The availability of techniques that allow the study of nondisjunction in sperm cells has permitted us to evaluate the possibility of an interchromosomal effect in male translocation heterozygotes. In this study, multicolor fluorescence in situ hybridization was used to determine levels of disomy for the clinically relevant chromosomes X, Y, 13, 18, and 21 in 332,858 spermatozoa from nine reciprocal translocation heterozygotes and nine controls with normal karyotypes. The specific translocations studied were as follows: t(10;12)(p26.1;p13.3), t(2;18)(p21;q11.2), t(3;19)(p25;q12), t(5;8)(q33;q13), t(11;22)(q23;q11), t(3;4)(p25;p16), t(8;9) (q24.2;q32), t(10;18)(q24.1;p11.2), and t(4;10)(q33;p12.2). Comparisons of disomy rates between carriers and controls were performed by using the Mann-Whitney test. Our results showed that the rates of sex chromosome hyperhaploidy were similar in controls (0.21%) and in translocation carriers (0.19%). Similarly, the frequencies of disomy for chromosomes 13, 18, and 21 did not differ significantly between controls and carriers (0.05% versus 0.08%, 0.07% versus 0.03%, and 0.14% versus 0.20%, respectively). Sex chromosome nondisjunction was more common than nondisjunction of chromosomes 13 and 18 both in controls (P=0.0057) and in carriers (P=0.0008). Similarly, the rates of chromosome disomy for chromosome 21 were higher than those for chromosomes 13 and 18 in both controls (P=0.0031) and translocation carriers (P=0.0057). In our study, the excess of chromosome 21 disomy versus disomy of the other autosomes was more pronounced in carriers than in controls. Thus, although the difference of disomy 21 between controls and carriers was not statistically significant, it is worthy of attention.

The effects of age and abnormal sperm count on the nondisjunction of spermatozoa.

The effect of paternal age on the nondisjunction of sex chromosomes is controversial. Also, the prevalence of chromosomal anomalies in infertile patients is controversial, it has been reported that the sex chromosomal aneuploidy rate following treatment with intracytoplasmic sperm injection (ICSI) is higher than in naturally conceived pregnancies. We investigated the influence of paternal age and oligozoospermia on the nondisjunction of spermatozoa. We determined the rate of aneuploidy for gonosomes and autosomes, using two-color fluorescence in situ hybridization (FISH) of the X and Y chromosomes and chromosomes 12 and 18 in 10 donors under 25 years of age who had a normal sperm count (> or = 20 x 10(6)/ml), 10 donors over the age of 39 years with idiopathic infertility and normozoospermia (> or = 20 x 10(6)/ml), and 5 oligozoospermic donors (< 20 x 10(6)/ml). There was no obvious relationship between increasing age and autosomal disomy (disomy 12 and disomy 18). Neither autosomal disomy nor diploidy was increased in any group. The frequency of X-, Y-, XX-, and YY-bearing sperm did not differ significantly among groups, but the frequency of XY-bearing sperm was significantly higher in the older infertile group than in the control donors. The incidence of nondisjunction of paternal sex chromosome in meiosis I was higher in older men with idiopathic infertility. The present results suggest that the risk of producing XXY fetuses is higher among men > 39 years of age with idiopathic infertility.

Aneuploidy and diploidy rates in sperm of five men after three-colour hybridization: indication of X chromosome-associated autosome 2 aneuploidy

The frequencies of aneuploidy and diploidy for chromosomes 2, X and Y in sperm nuclei of five nonsmoking normal donors were assessed by three-colour fluorescence in situ hybridization. We detected neither significant interindividual variability nor age effect (age range of the study group: 26–38 yr) on the mean frequencies of aneuploid and diploid sperm. Nullisomic sperm were observed more frequently than disomic sperm. In addition, sex chromosomal meiotic nondisjunction occurred at a higher rate than autosomal nondisjunction, and disomic sperm for the sex chromosomes were formed mainly by errors in the second meiotic division. Our data indicate that diploidy occurs at a very low frequency in comparison with aneuploidy. Furthermore, the overall proportion of X-bearing sperm nuclei aneuploid for chromosome 2 is significantly higher than that of Y-bearing sperm (0.14% vs. 0.05%, respectively; p<0.001). This finding adds further evidence that autosomal aneuploidy can be preferentially associated with the presence of one of the two gonosomes.

The effect of Y-chromosome alpha-satellite array length on the rate of sex chromosome disomy in human sperm.

Trisomy is the leading known cause of mental retardation and pregnancy loss in humans, yet virtually nothing is known of the underlying nondisjunctional mechanisms. Since studies of other organisms suggest an association between centromere size or sequence and meiotic nondisjunction, we recently initiated studies to examine the effect of centromere size variation on human nondisjunction. In the present report, we summarize studies correlating variation in the size of the Y-chromosome centromere with sex chromosome nondisjunction. In one set of studies, we used pulsed-field gel electrophoresis to estimate Y-chromosome alpha-satellite array lengths in normal males, and correlated these values with Y-chromosome sperm disomy levels as determined by fluorescence in situ hybridization. In a second set of studies, we determined the Y-chromosome alpha-satellite array length of 47,XYY males, since the karyotypes of these individuals are a consequence of Y chromosome nondisjunction. Neither set of studies provided evidence for an effect of Y-chromosome alpha-satellite array length on Y-chromosome nondisjunction. Thus, if there is an association between Y-chromosome centromere size and nondisjunction, the effect is subtle and below the detection levels of the present study or involves extreme size variants that were not represented in the present study population.

A selective method for studying primary sex chromosome non-disjunction in females and males and X-Y exchange in males of Drosophila melanogaster including a demonstration of euchromatic X-Y exchange.

A selective method was developed, based on negative complementation of the Abruptex alleles of the Notch locus, for studying primary sex chromosome non-disjunction in females and males of Drosophila melanogaster and X-Y exchange in males. The results show that the frequency of primary non-disjunction of structurally normal X chromosomes was lower than the frequency of X-derY non-disjunction in males. Double exchange between the X and the derY chromosome in the male occurs with a frequency of at least 0.091%. Single exchanges are naturally expected to occur with even higher frequency. Exchanges were interestingly at least partly of euchromatic nature. The origin of these exchanges is at least partly of gonial origin.

Patchy Fur (Paf), a Semidominant X-Linked Gene Associated with a High Level of X-Y Nondisjunction in Male Mice

Several X-linked mutations that have associated sex chromosomal nondisjunction have been identified in the mouse. We describe a new semidominant X-linked mutation called patchy fur (Paf) that produces an abnormal coat. It maps to the distal end of the murine X chromosome very near the XY pseudoautosomal region. The degree of severity in affected mice is hemizygous males greater than homozygous females greater than heterozygous females. An unusual feature of Paf is that either the mutation itself or an inseparable chromosomal abnormality causes delayed disjunction of the X and Y chromosomes at meiotic metaphase I, which in turn results in approximately 19% XO progeny and slightly less than 1% XXY progeny from Paf/Y males. The effect occurs only in male carriers and thus must extend into the proximal end of the XY pairing region.