Showing papers on "X chromosome published in 1991"
TL;DR: It is concluded that enlargement of the CAG repeat in the androgen receptor gene is probably the cause of X-LINKED spinal and bulbar muscular atrophy.
Abstract: X-linked spinal and bulbar muscular atrophy (Kennedy's disease) is an adult-onset form of motorneuron disease which may be associated with signs of androgen insensitivity. We have now investigated whether the androgen receptor gene on the proximal long arm of the X chromosome is a candidate gene for this disease. In patient samples we found androgen receptor gene mutations with increased size of a polymorphic tandem CAG repeat in the coding region. These amplified repeats were absolutely associated with the disease, being present in 35 unrelated patients and none of 75 controls. They segregated with the disease in 15 families, with no recombination in 61 meioses (the maximum log likelihood ratio (lod score) is 13.2 at a recombination rate of 0). The association is unlikely to be due to linkage disequilibrium, because 11 different disease alleles were observed. We conclude that enlargement of the CAG repeat in the androgen receptor gene is probably the cause of this disorder.
2,704 citations
TL;DR: It is shown that Sry on a 14-kilobase genomic DNA fragment is sufficient to induce testis differentiation and subsequent male development when introduced into chromosomally female mouse embryos.
Abstract: The initiation of male development in mammals requires one or more genes on the Y chromosome. A recently isolated gene, termed SRY in humans and Sry in mouse, has many of the genetic and biological properties expected of a Y-located testis-determining gene. It is now shown that Sry on a 14-kilobase genomic DNA fragment is sufficient to induce testis differentiation and subsequent male development when introduced into chromosomally female mouse embryos.
2,070 citations
TL;DR: expression of the fragile X syndrome appears to result from a two-step mutation as well as a highly localized methylation, and can easily be detected regardless of sex or phenotypic expression.
Abstract: The fragile X syndrome, a common cause of inherited mental retardation, is characterized by an unusual mode of inheritance. Phenotypic expression has been linked to abnormal cytosine methylation of...
1,479 citations
TL;DR: This gene, called XIST (for Xi-specific transcripts), is a candidate for a gene either involved in or uniquely influenced by the process of X inactivation, and is described as an X-linked gene with a novel expression pattern.
Abstract: X-chromosome inactivation results in the cis-limited dosage compensation of genes on one of the pair of X chromosomes in mammalian females. Although most X-linked genes are believed to be subject to inactivation, several are known to be expressed from both active and inactive X chromosomes. Here we describe an X-linked gene with a novel expression pattern--transcripts are detected only from the inactive X chromosome (Xi) and not from the active X chromosome (Xa). This gene, called XIST (for Xi-specific transcripts), is a candidate for a gene either involved in or uniquely influenced by the process of X inactivation.
1,397 citations
TL;DR: Structurally distinct sex chromosomes are the most familiar mode of genetic sex determination and have evolved independently in many different taxa and the evolutionary paths by which their characteristic properties may have evolved are reviewed.
Abstract: Structurally distinct sex chromosomes (X and Y) are the most familiar mode of genetic sex determination and have evolved independently in many different taxa. The evolutionary paths by which their characteristic properties may have evolved are reviewed. These properties include the failure of X and Y to recombine through much or all of their length, the genetic inertness of much of the Y chromosome, dosage compensation of the activity of X chromosomal loci, and the accumulation of repeated DNA sequences on the Y chromosome.
765 citations
TL;DR: This work has devised a method of identifying carriers of these mutations by direct DNA analysis and distinguished clearly in a single test between the normal genotype, the premutation, and the full mutation.
Abstract: Background. The fragile X syndrome, the most common form of inherited mental retardation, is caused by mutations that increase the size of a specific DNA fragment of the X chromosome (in Xq27.3). Affected persons have both a full mutation and abnormal DNA methylation. Persons with a smaller increase in the size of this DNA fragment (a premutation) have little or no risk of retardation but are at high risk of having affected children or grandchildren. The passage from premutation to full-mutation status occurs only with transmission from the mother. We have devised a method of identifying carriers of these mutations by direct DNA analysis. Method. We studied 511 persons from 63 families with the fragile X syndrome. Mutations and abnormal methylation were detected by Southern blotting with a probe adjacent to the mutation target. Analysis of EcoRI and EagI digests of DNA distinguished clearly in a single test between the normal genotype, the premutation, and the full mutation. Results. DNA analysis...
612 citations
TL;DR: Comparison of the human and rat genetic maps indicates that BP/SP-1 could reside on human chromosome 17q in a region that also contains the angiotensin l-converting enzyme gene (ACE)8, and is therefore a candidate gene in primary hypertension.
Abstract: The spontaneously hypertensive rat and the stroke-prone spontaneously hypertensive rat are useful models for human hypertension. In these strains hypertension is a polygenic trait, in which both autosomal and sex-linked genes can influence blood pressure. Linkage studies in crosses between the stroke-prone spontaneously hypertensive rat and the normotensive control strain Wistar-Kyoto have led to the localization of two genes, BP/SP-1 and BP/SP-2, that contribute significantly to blood pressure variation in the F2 population. BP/SP-1 and BP/SP-2 were assigned to rat chromosomes 10 and X, respectively. Comparison of the human and rat genetic maps indicates that BP/SP-1 could reside on human chromosome 17q in a region that also contains the angiotensin I-converting enzyme gene (ACE). This encodes a key enzyme of the renin-angiotensin system, and is therefore a candidate gene in primary hypertension. A rat microsatellite marker of ACE was mapped to rat chromosome 10 within the region containing BP/SP-1.
611 citations
TL;DR: Conservation between man and mouse of chromosomal position and unique expression exclusively from the inactive X chromosome lends support to the hypothesis that XIST and its mouse homologue are involved in X-chromosome inactivation.
Abstract: X-chromosome inactivation in mammals is a regulatory phenomenon whereby one of the two X chromosomes in female cells is genetically inactivated, resulting in dosage compensation for X-linked genes between males and females. In both man and mouse, X-chromosome inactivation is thought to proceed from a single cis-acting switch region or inactivation centre (XIC/Xic). In the human, XIC has been mapped to band Xq13 (ref. 6) and in the mouse to band XD (ref. 7), and comparative mapping has shown that the XIC regions in the two species are syntenic. The recently described human XIST gene maps to the XIC region and seems to be expressed only from the inactive X chromosome. We report here that the mouse Xist gene maps to the Xic region of the mouse X chromosome and, using an interspecific Mus spretus/Mus musculus domesticus F1 hybrid mouse carrying the T(X;16)16H translocation, show that Xist is exclusively expressed from the inactive X chromosome. Conservation between man and mouse of chromosomal position and unique expression exclusively from the inactive X chromosome lends support to the hypothesis that XIST and its mouse homologue are involved in X-chromosome inactivation.
604 citations
TL;DR: The isolation and characterization of its murine homologue (Xist) is reported which localizes to the mouse X inactivation centre region and is the first murine gene found to be expressed from the inactive X chromosome and may be associated with a protein product.
Abstract: IN mammals, equal dosage of gene products encoded by the X chromosome in male and female cells is achieved by X inactivation. Although X-chromosome inactivation represents the most extensive example known of long range cis gene regulation, the mechanism by which thousands of genes on only one of a pair of identical chromosomes are turned off is poorly understood. We have recently identified a human gene (XIST) exclusively expressed from the inactive X chromosome1. Here we report the isolation and characterization of its murine homologue (Xist) which localizes to the mouse X inactivation centre region and is the first murine gene found to be expressed from the inactive X chromosome. Nucleotide sequence analysis indicates that Xist may be associated with a protein product. The similar map positions and expression patterns for Xist in mouse and man suggest that this gene may have a role in X inactivation.
525 citations
TL;DR: Two de novo insertions of truncated L1 elements into the factors VIII gene on the X chromosome have been identified that produced hemophilia A and a full-length L1 element that is the likely progenitor of one of these insertions was isolated by its sequence identity to the factor VIII insertion.
Abstract: Two de novo insertions of truncated L1 elements into the factor VIII gene on the X chromosome have been identified that produced hemophilia A. A full-length L1 element that is the likely progenitor of one of these insertions was isolated by its sequence identity to the factor VIII insertion. This L1 element contains two open-reading frames and is one of at least four alleles of a locus on chromosome 22 that has been occupied by an L1 element for at least 6 million years.
424 citations
TL;DR: An analysis of several rearranged human X chromosomes is reported and a minimal region of overlap is defined that is consistent with models invoking a single XIC and provide a molecular foothold for cloning and analysing the XIC region.
Abstract: X-CHROMOSOME inactivation results in the strictly cis-limited inactivation of many but not all genes on one of the two X chromosomes during early development in somatic cells of mammalian females1. One feature of virtually all models of X inactivation is the existence of an X-inactivation centre (XIC) required in cis for inactivation to occur2–5. This concept predicts that all structurally abnormal X chromosomes capable of being inactivated have in common a defineable region of the X chromosome6–8. Here we report an analysis of several such rearranged human X chromosomes and define a minimal region of overlap. The results are consistent with models invoking a single XIC and provide a molecular foothold for cloning and analysing theXIC region. One of the markers that defines this region is theXIST gene9, which is expressed specifically from inactive, but not active, X chromosomes. The localization of the XIST gene to theXIC region on the human X chromosome implicates XIST in some aspect of X inactivation.
TL;DR: There is no simple relationship between the degree of methylation and either the level of expression of the fragile site or the severity of the clinical phenotype in the fragile X syndrome.
TL;DR: The maleless (mle) gene is one of four known regulatory loci required for increased transcription (dosage compensation) of X-linked genes in D. melanogaster males and a strong candidate to be a direct regulator of dosage compensation.
TL;DR: The myeloproliferative syndromes are acquired disorders of hematopoiesis that provide insights into the transition from somatic cell mutation to neoplasia and the PCR technique is used to demonstrate heterogeneity of lineage involvement in patients with PCV.
Abstract: The myeloproliferative syndromes are acquired disorders of hematopoiesis that provide insights into the transition from somatic cell mutation to neoplasia. The clonal origin of specific blood cells can be assessed in patients with X chromosome-linked polymorphisms, taking advantage of random inactivation of the X chromosome. We have adapted the PCR for determination of clonality on as few as 100 cells, including individual colonies grown in culture. Amplifying a polymorphic portion of the X chromosome-linked phosphoglycerate kinase (PGK) gene after selective digestion of the active X chromosome with a methylation-sensitive restriction enzyme gave results fully concordant with standard Southern blotting of DNA samples from normal (polyclonal) polymorphonuclear cells (PMN) as well as clonal PMN from patients with myelodysplastic syndrome and polycythemia vera (PCV). We have used this technique to demonstrate heterogeneity of lineage involvement in patients with PCV. The same clinical phenotype may arise from clonal proliferation of different hematopoietic progenitors.
Journal Article•
TL;DR: A screening of all non-acrocentric chromosome arms, including those of the X chromosome, with at least one polymorphic marker per arm, in a total of 86 breast carcinomas indicates that in addition to the chromosome regions listed above, allelic loss may be observed in more than 30% of informative cases on 6q, 8q, 9q, 15q, and 16q.
Abstract: Loss of heterozygosity (LOH), which is detected with polymorphic DNA markers by comparing constitutional and tumor genotypes, has been observed at a number of different chromosome arms in primary breast tumors. These include 1p, 1q, 3p, 11p, 13q, 17p and 18q. We present here the results of a screening of all non-acrocentric chromosome arms, including those of the X chromosome, with at least one polymorphic marker per arm, in a total of 86 breast carcinomas. This dataset, termed an allelotype, indicates that in addition to the chromosome regions listed above, allelic loss may be observed in more than 30% of informative cases on 6q, 8q, 9q, 15q, and 16q. Multiple LOH involving at least two different chromosomes in a single tumor was observed in approximately 75% of the investigated tumors, and revealed complex chromosome involvement. Six different combinations of concurrent LOH at two different chromosome arms were found to be significantly correlated (r greater than 0.45; P less than 0.01). Tumors showing LOH at 3p or 17p were preferentially aneuploid, while LOH at 6q and 17q was inversely correlated with the number of positive lymph nodes and age respectively.
TL;DR: To detect rearrangements, or methylation changes that may reflect a locally inactive X chromosome, pulsed-field gel analysis of DNA from fragile-X patients with probes close to the fragile- X locus was used.
Abstract: THE fragile-X syndrome is the most frequent inherited form of mental retardation, with an incidence of 1 in 1,500 males. It is characterized by the presence of a fragile site at Xq27.3 induced in vitro by folate deprivation or by inhibitors of deoxynucleotide synthesis1. Its mode of inheritance is unusual for an X-linked trait, with incomplete penetrance in both males and females. Some phenotypically normal males transmit the mutation to all their daughters who rarely express any symptoms, but penetrance is high in sons and daughters of these carrier women2. Genetic and physical mapping of the Xq27-q28 region has confirmed that the disease locus is located at or very near the fragile site3–6. Hypotheses proposed to account for the abnormalities in the inheritance of the disease include sequence rearrangements by meiotic recombination1,7,8 or a mutation that affects reactivation of an inactive X chromosome during differentiation of female germ cells9,10. To detect such rearrangements, or methylation changes that may reflect a locally inactive X chromosome, we used pulsed-field gel analysis of DNA from fragile-X patients with probes close to the fragile-X locus. The probe Do33 (DXS465) detected abnormal patterns in fragile-X patients, but not in normal controls or in non-expressing male transmitters.
TL;DR: The results suggest that a senescence gene or genes, which may be located on the Chinese hamster X chromosome, can be regulated by DNA methylation, and that escape from senescing activity and possibly loss of tumor suppressor gene activity can occur by epigenetic mechanisms.
Abstract: Transfer of a normal Chinese hamster X chromosome (carried in a mouse A9 donor cell line) to a nickel-transformed Chinese hamster cell line with an Xq chromosome deletion resulted in senescense of these previously immortal cells. At early passages of the A9/CX donor cells, the hamster X chromosome was highly active, inducing senescence in 100% of the colonies obtained after its transfer into the nickel-transformed cells. However, senescence was reduced to 50% when Chinese hamster X chromosomes were transferred from later passage A9 cells. Full senescing activity of the intact hamster X chromosome was restored by treatment of the donor mouse cells with 5-azacytidine, which induced demethylation of DNA. These results suggest that a senescence gene or genes, which may be located on the Chinese hamster X chromosome, can be regulated by DNA methylation, and that escape from senescence and possibly loss of tumor suppressor gene activity can occur by epigenetic mechanisms.
TL;DR: Cytogenetic evidence from one of these cell lines suggests that chromosome breakage with healing at the integration site is the mechanism responsible for the terminal location of telomeres in yeast.
Abstract: Telomeric sequences of eukaryotes consist of short tandem repeats organized in arrays of variable length in which the guanine-rich strand runs 5'----3' toward the chromosomal end. The terminal repeats in yeast are the only elements necessary for telomere function in this organism. To test whether mammalian terminal repeats can function after reintroduction into a mammalian cell, a repeat-containing terminal fragment from a human chromosome was electroporated into a hamster-human hybrid cell line. In 6 of 27 independent transformants analyzed, the introduced sequences were found at the ends of chromosomes, based on all available criteria. Terminal restriction-fragment heterogeneity and the survival of these chromosomes demonstrate that these telomeres are functional. Cytogenetic evidence from one of these cell lines suggests that chromosome breakage with healing at the integration site is the mechanism responsible for the terminal location.
TL;DR: A single CpG island was identified in the cloned region between markers DXS463 and DXS465 that appears methylated in mentally retarded fragile X males, but not in nonexpressing male carriers of the mutation nor in normal males.
Abstract: Yeast artificial chromosomes (YACs) were obtained from a 550-kilobase region that contains three probes previously mapped as very close to the locus of the fragile X syndrome. These YACs spanned the fragile site in Xq27.3 as shown by fluorescent in situ hybridization. An internal 200-kilobase segment contained four chromosomal breakpoints generated by induction of fragile X expression. A single CpG island was identified in the cloned region between markers DXS463 and DXS465 that appears methylated in mentally retarded fragile X males, but not in nonexpressing male carriers of the mutation nor in normal males. This CpG island may indicate the presence of a gene involved in the clinical phenotype of the syndrome.
Journal Article•
TL;DR: It is concluded that most paternally derived 47,XXYs result from meiosis in which the X and Y chromosomes did not recombine, which is significantly shorter than the normal male map of the pseudoautosomal region.
Abstract: To assess the possible association between aberrant recombination and XY chromosome nondisjunction, we compared pseudoautosomal region recombination rates in male meiosis resulting in 47,XXY offspring with those resulting in 46,XY and 46,XX offspring. Forty-one paternally derived 47,XXYs and their parents were tested at six polymorphic loci spanning the pseudoautosomal region. We were able to detect crossing-over in only six of 39 cases informative for the telomeric DXYS14/DXYS20 locus. Subsequently, we used the data to generate a genetic linkage map of the pseudoautosomal region and found it to be significantly shorter than the normal male map of the region. From these analyses we conclude that most paternally derived 47,XXYs result from meiosis in which the X and Y chromosomes did not recombine.
TL;DR: The two-locus analytic method is extended and it is demonstrated that a proportion of affected females are likely heterozygous at the X chromosome-linked locus and are affected due to unfortunate X chromosome inactivation, thus providing an explanation for the later age of onset in females.
Abstract: Leber hereditary optic neuropathy (LHON) has been shown to involve mutation(s) of mitochondrial DNA, yet there remain several confusing aspects of its inheritance not explained by mitochondrial inheritance alone, including male predominance, reduced penetrance, and a later age of onset in females. By extending segregation analysis methods to disorders that involve both a mitochondrial and a nuclear gene locus, we show that the available pedigree data for LHON are most consistent with a two-locus disorder, with one responsible gene being mitochondrial and the other nuclear and X chromosome-linked. Furthermore, we have been able to extend the two-locus analytic method and demonstrate that a proportion of affected females are likely heterozygous at the X chromosome-linked locus and are affected due to unfortunate X chromosome inactivation, thus providing an explanation for the later age of onset in females. The estimated penetrance for a heterozygous female is 0.11 +/- 0.02. The calculated frequency of the X chromosome-linked gene for LHON is 0.08. Among affected females, 60% are expected to be heterozygous, and the remainder are expected to be homozygous at the responsible X chromosome-linked locus.
TL;DR: The isolation of a new testis-specific gene, Sby, mapping to the DNA deleted from the Sxrb region (the ΔSxrb interval), which has extensive homology to the X-linked human ubiquitin-activating enzyme El.
Abstract: THE Sxr (sex-reversed) region, a fragment of the Y chromosome short arm, can cause chromosomally female XXSxr or XSxrO mice to develop as sterile males1–3. The original Sxr region, termed Sxra, encodes: Tdy, the primary sex-determining gene; Hya, the controlling or structural locus for the minor transplantation antigen H–Y (ref. 4); gene(s) controlling the expression of the serologically detected male antigen (SDMA)5; Spy, a gene(s) required for the survival and proliferation of A spermatogonia during spermatogenesis6,7; Zfy-l/Zfy-2, zinc-finger-containing genes of unknown function8; and Sry, which is probably identical to Tdy (ref. 9). A deletion variant10 of Sxra, termed Sxrb, which lacks Hya, SDMA expression, Spy and some Zfy-2 sequences, makes positional cloning of these genes possible. We report here the isolation of a new testis-specific gene, Sby, mapping to the DNA deleted from the Sxrb region (the ΔSxrb interval). Sby has extensive homology to the X-linked human ubiquitin-activating enzyme El (ref. 11). The critical role of this enzyme in nuclear DNA replication12 together with the testis-specific expression of Sby suggests Sby as a candidate for the spermatogenic gene Spy.
TL;DR: The isolation, characterization, and chromosomal mapping of two human steroid 5 alpha-reductase genes are reported, one of which is functional, contains five exons separated by four introns, and maps to the distal short arm of chromosome 5.
TL;DR: A system to analyse whether specific genes on the mouse X chromosome are inactivated, and demonstrate that both ZFX and RPS4X undergo normal X-inactivation in mice, which may explain the relative viability of XO mice compared to XO humans.
Abstract: ONLY about 1% of human XO conceptuses survive to birth and these usually have the characteristics of Turner's syndrome, with a complex and variable phenotype including short stature, gonadal dysgenesis and anatomical defects1. Both the embryonic lethality and Turner's syndrome are thought to be due to monosomy for a gene or genes common to the X and Y chromosomes2. These genes would be expected to be expressed in females from both active and inactive X chromosomes to ensure correct dosage of gene product. Two genes with these properties are ZFX and RPS4X, both of which have been proposed to play a role in Turner's syndrome3,4. In contrast to humans, mice that are XO are viable with no prenatal lethality (P. Burgoyne, personal communication) and are anatomically normal and fertile. We have devised a system to analyse whether specific genes on the mouse X chromosome are inactivated, and demonstrate that both Zfx and Rps4X undergo normal X-inactivation in mice. Thus the relative viability of XO mice compared to XO humans may be explained by differences between the two species in the way that dosage compensation of specific genes is achieved.
TL;DR: Recovery of equal numbers of recombinant and nonrecombinant offspring from XY* males supports the hypothesis that recombination between the mammalian X and Y chromosomes is necessary for primary spermatocytes to successfully complete sperMatogenesis and form functional sperm.
Abstract: Cytological analysis of the mouse Y* chromosome revealed a complex rearrangement involving acquisition of a functional centromere and centromeric heterochromatin and attachment of this chromosomal segment to the distal end of a normal Y* chromosome. This rearrangement positioned the Y* short-arm region at the distal end of the Y* chromosome and the pseudoautosomal region interstitially, just distal to the newly acquired centromere. In addition, the majority of the pseudoautosomal region was inverted. Recombination between the X and the Y* chromosomes generates two new sex chromosomes: (1) a large chromosome comprised of the X chromosome attached at its distal end to all of the Y* chromosome but missing the centromeric region (XY*) and (2) a small chromosome containing the centromeric portion of the Y* chromosome attached to G-band-negative material from the X chromosome (YX). Mice that inherit the XY* chromosome develop as sterile males, whereas mice that inherit the Y*X chromosome develop as fertile females. Recovery of equal numbers of recombinant and nonrecombinant offspring from XY* males supports the hypothesis that recombination between the mammalian X and Y chromosomes is necessary for primary spermatocytes to successfully complete spermatogenesis and form functional sperm.
TL;DR: The mouse Als9 gene is isolated, mapped it to the proximal portion of the X chromosome and shown that it undergoes normal X-inactivation, and is a candidate for the spermatogenesis gene, Spy, which maps to this region.
Abstract: THE human X-linked gene A1S9 (refs 1–3) complements a temperature-sensitive cell-cycle mutation in mouse L cells4, and encodes the ubiquitin-activating enzyme El (refs 5–7). The gene has been reported to escape X-chromosome inactivation8, but there is some conflicting evidence9. We have isolated part of the mouse Als9 gene, mapped it to the proximal portion of the X chromosome and shown that it undergoes normal X-inactivation. We alsodetected two copies of the gene on the short arm of the mouse Y chromosome (Als9Y-l and Als9Y-2). The functional Als9Y gene (Als9Y-l) is expressed in testis and is lost in the deletion mutant Sxrb (ref. 10). Therefore Als9Y-l is a candidate for the sper-matogenesis gene, Spy, which maps to this region. Als9X is similar to the Zfx gene in undergoing X-inactivation11,12, yet having homologous sequences on the short arm of the Y chromosome13,14, which are expressed in the testis. These Y-linked genes may form part of a coregulated group of genes which function during spermatogenesis.
TL;DR: Comparison of the structures of connexin genes suggests that members of this multigene family arose from a single precursor, but evolved to distinct chromosomal locations.
TL;DR: The correlation between the patient' phenotypes and the extent of their Yq11 deletions permits the tentative assignment of a locus involved in human spermatogenesis to a specific interval within Y Q11, suggesting the present organization of this region of the human Y chromosome is due to three physically and temporary distinct rearrangements.
TL;DR: Preliminary data suggest that young females who show preferential presence of a full mutation on the active X in leucocytes may be at increased risk for mental retardation, and preliminary evidence for an age dependent decrease in the somatic heterogeneity of full mutations is obtained.
Abstract: We have studied the patterns of mutation and X inactivation in female carriers of a fragile X mutation, to try to correlate them with various phenotypic features. We used a simple assay, which shows simultaneously the size of the mutation, its methylation status, and DNA fragments that represent the normal active and inactive X chromosomes. We have observed an age dependent process, whereby the 'full' fragile X mutation is found preferentially on the inactive X in leucocytes in adult females, but not in younger ones. This phenomenon was not observed in female carriers of a 'premutation', who have little phenotypic expression. Preliminary data suggest that young females who show preferential presence of a full mutation on the active X in leucocytes may be at increased risk for mental retardation. We have also obtained preliminary evidence for an age dependent decrease in the somatic heterogeneity of full mutations, possibly owing to selection for smaller mutated fragments. If confirmed, the latter phenomenon might account for the known decrease with age of the expression of the fragile site. Our observations suggest that a gene whose expression is affected by the presence of a full mutation (possibly the FMR-1 gene) has a cell autonomous function in leucocytes, leading to a slowly progressive selection for cells where the mutation is on the inactive X chromosome.
Journal Article•
TL;DR: The ratio of maternal X to paternal X is just over 2:1, which is consistent with the expected proportion of meiotic or mitotic products, with equal loss at each step, given the nonviability of 45,Y.
Abstract: We have used X- and Y-linked RFLPs to determine the origin of the single X chromosome in 25 live-born individuals with Turner syndrome. We determined that 18 individuals retained a maternal X (Xm) and that seven retained the paternal X (Xp). No occult mosaicism was detected. We found no differences in either maternal or paternal ages for the two groups. The ratio of maternal X to paternal X is just over 2:1, which is consistent with the expected proportion of meiotic or mitotic products, with equal loss at each step, given the nonviability of 45,Y. Six phenotypic or physiologic characteristics were assessed: (1) birth weight, (2) height percentile at time of testing, (3) presence of a webbed neck, (4) cardiovascular abnormalities, (5) renal abnormalities, and (6) thyroid autoimmunity. There were no significant differences in birth weights or heights between the girls who retained the maternal X or the paternal X. In addition, no differences between the groups could be appreciated in the incidence of the physical, anatomic, or physiologic parameters assessed.