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Segregation analysis of a sex ratio distortion locus in congenic mice.

ABSTRACT: The congenic HG.CAST-(D17Mit196-D17Mit190) (HQ17(hg/hg)) mouse strain showed a significant departure on the expected 50%/50% offspring sex ratio in more than 2400 progeny (55.7% females). The entire pedigree file included data from 13 nonoverlapping purebred generations and an F(2) cross with the C57BL/6J inbred strain. Offspring sex ratio data were analyzed on the basis of 40 purebred HQ17(hg)(/hg) sires and 29 F(1) HQ17(hg)(/hg) x B6 sires under a Bayesian Binomial segregation model accounting for 4 different autosomal inheritance models of gene action (i.e., additive, dominance, recessive, and overdominance) and X-linked and Y-linked loci. For each model, the segregation effect was evaluated as a single regression coefficient for all sires or assuming 2 independent regression coefficients accounting for offspring sex ratio departures in purebred and F(1) sires, respectively. The deviance information criterion clearly favored the autosomal dominance model with different regression coefficients for the 2 groups of sires. Under this model, the dominance effect increased the percentage of female offspring by 4.3% (HQ17(hg)(/hg) purebred sires) and 8.2% (F(1) sires) with the highest posterior density regions ranging from 0.5% to 10.6% and from 1.3% to 14.4%, respectively. This article provides significant evidence of genetic determinism for sex ratio distortion in the HQ17(hg)(/hg) strain and develops new analytical tools to perform segregation studies on dichotomous traits.

SUBMITTER: Casellas J

PROVIDER: S-EPMC2855675 | biostudies-literature | 2010 May-Jun

REPOSITORIES: biostudies-literature

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Segregation analysis of a sex ratio distortion locus in congenic mice.

Casellas Joaquim J Farber Charles R CR Verdugo Ricardo A RA Medrano Juan F JF

The Journal of heredity 20091223 3

The congenic HG.CAST-(D17Mit196-D17Mit190) (HQ17(hg/hg)) mouse strain showed a significant departure on the expected 50%/50% offspring sex ratio in more than 2400 progeny (55.7% females). The entire pedigree file included data from 13 nonoverlapping purebred generations and an F(2) cross with the C57BL/6J inbred strain. Offspring sex ratio data were analyzed on the basis of 40 purebred HQ17(hg)(/hg) sires and 29 F(1) HQ17(hg)(/hg) x B6 sires under a Bayesian Binomial segregation model accounting ...[more]

PMID: 20032064

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Project description:BackgroundWhile transmission ratio distortion, TRD, (a deviation from Mendelian ratio) is extensive in humans and well-documented in mice, the underlying mechanisms are unknown. Our earlier studies on carriers of spontaneous mutations of mouse Sperm Adhesion Molecule 1 (Spam1) suggested that TRD results from biochemically different sperm, due to a lack of transcript sharing through the intercellular cytoplasmic bridges of spermatids. These bridges usually allow transcript sharing among genetically different spermatids which develop into biochemically and functionally equivalent sperm.ObjectivesThe goals of the study were to provide support for the lack of sharing (LOS) hypothesis, using transgene and null carriers of Spam1, and to determine the mechanism of Spam1-associated TRD.MethodsCarriers of Spam1-Hyal5 BAC transgenes were mated with wild-type female mice and the progeny analyzed for TRD by PCR genotyping. Sperm from transgene and Spam1 null carriers were analyzed using flow cytometry and immunocytochemistry to detect quantities of Spam1 and/or Hyal5. Transgene-bearing sperm with Spam1 overexpression were detected by fluorescence in situ hybridization. In wild-type animals, EM studies of in situ transcript hybridization of testis sections and Northern analysis of biochemically fractionated testicular RNA were performed to localize Spam1 transcript. Finally, AU-rich motifs identified in the 3' UTR of Spam1 RNA were assayed by UV cross-linking to determine their ability to interact with testicular RNA binding proteins.ResultsThe Tg8 line of transgene carriers had a significant (P < 0.001) TRD, due to reduced fertilizing ability of transgene-bearing sperm. These sperm retained large cytoplasmic droplets engorged with overexpressed Spam1 or Hyal5 protein. Caudal sperm from transgene carriers and caput sperm of null carriers showed a bimodal distribution of Spam1, indicating that the sperm in a male were biochemically different with respect to Spam1 quantities. Spam1 RNA was absent from the bridges, associated exclusively with the ER, and was shown to be anchored to the cytoskeleton. This compartmentalization of the transcript, mediated by cytoskeletal binding, occurs via protein interactions with 3' UTR AU-rich sequences that are likely involved in its stabilization.ConclusionWe provide strong support for the LOS hypothesis, and have elucidated the mechanism of Spam1-associated TRD.

Dataset Information

Segregation analysis of a sex ratio distortion locus in congenic mice.

Publications

Segregation analysis of a sex ratio distortion locus in congenic mice.

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