Non–mendelian inheritance of X chromosome markers in interspecific backcrosses

Abstract A fundamental principle of Mendelian inheritance is random segregation of alleles to progeny; however, examples of distorted transmission either of specific alleles or of whole chromosomes have been described in a variety of species. In humans and mice, a distortion in chromosome transmission is often associated with a chromosome abnormality. One such example is the fertile XO female mouse. A transmission distortion effect that results in an excess of XX over XO daughters among the progeny of XO females has been recognized for nearly four decades. Utilizing contemporary methodology that combines immunofluorescence, FISH, and three-dimensional confocal microscopy, we have readdressed the meiotic segregation behavior of the single X chromosome in oocytes from XO females produced on two different inbred backgrounds. Our studies demonstrate that segregation of the univalent X chromosome at the first meiotic division is nonrandom, with preferential retention of the X chromosome in the oocyte in ∼60% of cells. We propose that this deviation from Mendelian expectations is facilitated by a spindle-mediated mechanism. This mechanism, which appears to be a general feature of the female meiotic process, has implications for the frequency of nondisjunction in our species.

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Epistatic Control of Non-Mendelian Inheritance in Mouse Interspecific Crosses

Genetics ◽

10.1093/genetics/143.4.1739 ◽

1996 ◽

Vol 143 (4) ◽

pp. 1739-1752 ◽

Cited By ~ 2

Author(s):

Xavier Montagutelli ◽

Rowena Turner ◽

Joseph H Nadeau

Keyword(s):

X Chromosome ◽

Genetic Basis ◽

Mendelian Inheritance ◽

The Other ◽

Interspecific Crosses ◽

Chromosome 2 ◽

Mus Spretus ◽

F1 Hybrid ◽

Strong Deviation ◽

Marker Loci

Abstract Strong deviation of allele frequencies from Mendelian inheritance favoring Mus spretus-derived alleles has been described previously for X-linked loci in four mouse interspecific crosses. We reanalyzed data for three of these crosses focusing on the location of the gene(s) controlling deviation on the X chromosome and the genetic basis for incomplete deviation. At least two loci control deviation on the X chromosome, one near Xist (the candidate gene controlling X inactivation) and the other more centromerically located. In all three crosses, strong epistasis was found between loci near Xist and marker loci on the central portion of chromosome 2. The mechanism for this deviation from Mendelian expectations is not yet known but it is probably based on lethality of embryos carrying particular combinations of alleles rather than true segregation distortion during oogenesis in F1 hybrid females.

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Loci of intestinal distress in cystic fibrosis knockout mice

Physiological Genomics ◽

10.1152/physiolgenomics.00114.2002 ◽

2003 ◽

Vol 12 (2) ◽

pp. 79-84 ◽

Cited By ~ 15

Author(s):

Christina K. Haston ◽

Lap-Chee Tsui

Keyword(s):

Cystic Fibrosis ◽

X Chromosome ◽

Knockout Mice ◽

Mendelian Inheritance ◽

Genetic Dissection ◽

Male Mice ◽

Female Mice ◽

Genome Wide ◽

A Genome ◽

Strain Dependent

The strain-dependent survival of cystic fibrosis (CF) knockout mice has been used to map a modifier of CF, Cfm1, in mice and, subsequently, in humans. To identify additional modifiers of the CF phenotype, in this study, the survival of F2 CF mice derived from a cross between congenic C57BL/6J CF and BALB/cJ CF heterozygotes was followed up to 12 wk of age. A genome-wide linkage scan completed in F2 CF mice revealed a chromosome 10 locus ( P = 1.2 × 10−4) to predict for intestinal distress in CF male mice. An X chromosome locus for which non-Mendelian inheritance favoring B6 alleles in the surviving CF mice and BALB alleles in mice of a control population, was identified. The survival of female mice, both F2 CF and F2 control, was linked to loci on chromosomes 3 and 5. The identification of additional putative CF modifier loci may permit further genetic dissection of the complex CF phenotype.

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X-Chromosome Markers

Encyclopedia of Forensic Sciences ◽

10.1016/b978-0-12-382165-2.00047-7 ◽

2013 ◽

pp. 257-263

Author(s):

V. Pereira ◽

L. Gusmão

Keyword(s):

X Chromosome ◽

Chromosome Markers

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Population data of four x-chromosome markers in Tuscany and their use in a deficiency paternity case

Forensic Science International ◽

10.1016/s0379-0738(03)00361-x ◽

2003 ◽

Vol 137 (2-3) ◽

pp. 215-216 ◽

Cited By ~ 4

Keyword(s):

X Chromosome ◽

Population Data ◽

Chromosome Markers ◽

Paternity Case

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Mapping of a syndrome of X-linked thrombocytopenia with thalassemia to band Xp11-12: further evidence of genetic heterogeneity of X-linked thrombocytopenia

Blood ◽

10.1182/blood.v95.7.2262.007k32_2262_2268 ◽

2000 ◽

Vol 95 (7) ◽

pp. 2262-2268

Author(s):

Wendy H. Raskind ◽

Kathy K. Niakan ◽

John Wolff ◽

Mark Matsushita ◽

Ty Vaughan ◽

...

Keyword(s):

X Chromosome ◽

Mononuclear Cells ◽

Mendelian Inheritance ◽

Allelic Variant ◽

Accession Number ◽

Peripheral Blood Mononuclear ◽

Platelet Morphology ◽

Inactivation Pattern ◽

Chain Synthesis ◽

Mutation Analyses

X-linked thrombocytopenia with thalassemia (XLTT; Online Mendelian Inheritance in Man [OMIM] accession number 314050) is a rare disorder characterized by thrombocytopenia, platelet dysfunction, splenomegaly, reticulocytosis, and unbalanced hemoglobin chain synthesis. In a 4-generation family, the gene responsible for XLTT was mapped to the X chromosome, short arm, bands 11-12 (band Xp11-12). The maximum lod score possible in this family, 2.39, was obtained for markers DXS8054 and DXS1003, at a recombination fraction of 0. Recombination events observed for XLTT and markers DXS8080 and DXS8023 or DXS991 define a critical region that is less than or equal to 7.65 KcM and contains the gene responsible for the Wiskott-Aldrich syndrome (WAS; OMIM accession number 301000) and its allelic variant X-linked thrombocytopenia (XLT; OMIM accession number 313900). Manifestations of WAS include thrombocytopenia, eczema, and immunodeficiency. In WAS/XLT the platelets are usually small, and bleeding is proportional to the degree of thrombocytopenia. In contrast, in XLTT the platelet morphology is normal, and the bleeding time is disproportionately prolonged. In this study no alteration in the WAS gene was detected by Northern blot or Western blot analysis, flow cytometry, or complimentary DNA dideoxynucleotide fingerprinting or sequencing. As has been reported for WAS and some cases of XLT, almost total inactivation of the XLTTgene-bearing X chromosome was observed in granulocytes and peripheral blood mononuclear cells from 1 asymptomatic obligate carrier. The XLTT carrier previously found to have an elevated :β hemoglobin chain ratio had a skewed, but not clonal, X-inactivation pattern favoring activity of the abnormal allele. Clinical differences and results of the mutation analyses make it very unlikely that XLTT is another allelic variant of WAS/XLT and strongly suggest that X-linked thrombocytopenia mapping to band Xp11-12 is a genetically heterogeneous disorder.

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