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Refined mapping of a quantitative trait locus on chromosome 1 responsible for mouse embryonic death.

ABSTRACT: Recurrent spontaneous abortion (RSA) is defined as the loss of three or more consecutive pregnancies during the first trimester of embryonic intrauterine development. This kind of human infertility is frequent among the general population since it affects 1 to 5% of women. In half of the cases the etiology remains unelucidated. In the present study, we used interspecific recombinant congenic mouse strains (IRCS) in the aim to identify genes responsible for embryonic lethality. Applying a cartographic approach using a genotype/phenotype association, we identified a minimal QTL region, of about 6 Mb on chromosome 1, responsible for a high rate of embryonic death (?30%). Genetic analysis suggests that the observed phenotype is linked to uterine dysfunction. Transcriptomic analysis of the uterine tissue revealed a preferential deregulation of genes of this region compared to the rest of the genome. Some genes from the QTL region are associated with VEGF signaling, mTOR signaling and ubiquitine/proteasome-protein degradation pathways. This work may contribute to elucidate the molecular basis of a multifactorial and complex human disorder as RSA.

SUBMITTER: Vatin M

PROVIDER: S-EPMC3420870 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Refined mapping of a quantitative trait locus on chromosome 1 responsible for mouse embryonic death.

Vatin Magalie M Burgio Gaetan G Renault Gilles G Laissue Paul P Firlej Virginie V Mondon Françoise F Montagutelli Xavier X Vaiman Daniel D Serres Catherine C Ziyyat Ahmed A

PloS one 20120816 8

Recurrent spontaneous abortion (RSA) is defined as the loss of three or more consecutive pregnancies during the first trimester of embryonic intrauterine development. This kind of human infertility is frequent among the general population since it affects 1 to 5% of women. In half of the cases the etiology remains unelucidated. In the present study, we used interspecific recombinant congenic mouse strains (IRCS) in the aim to identify genes responsible for embryonic lethality. Applying a cartogr ...[more]

PMID: 22916247

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Project description:BACKGROUND: A major QTL for fatness and growth, denoted FAT1, has previously been detected on pig chromosome 4q (SSC4q) using a Large White - wild boar intercross. Progeny that carried the wild boar allele at this locus had higher fat deposition, shorter length of carcass, and reduced growth. The position and the estimated effects of the FAT1 QTL for growth and fatness have been confirmed in a previous study. In order to narrow down the QTL interval we have traced the inheritance of the wild boar allele associated with high fat deposition through six additional backcross generations. RESULTS: Progeny-testing was used to determine the QTL genotype for 10 backcross sires being heterozygous for different parts of the broad FAT1 region. The statistical analysis revealed that five of the sires were segregating at the QTL, two were negative while the data for three sires were inconclusive. We could confirm the QTL effects on fatness/meat content traits but not for the growth traits implying that growth and fatness are controlled by distinct QTLs on chromosome 4. Two of the segregating sires showed highly significant QTL effects that were as large as previously observed in the F2 generation. The estimates for the remaining three sires, which were all heterozygous for smaller fragments of the actual region, were markedly smaller. With the sample sizes used in the present study we cannot with great confidence determine whether these smaller effects in some sires are due to chance deviations, epistatic interactions or whether FAT1 is composed of two or more QTLs, each one with a smaller phenotypic effect. Under the assumption of a single locus, the critical region for FAT1 has been reduced to a 3.3 cM interval between the RXRG and SDHC loci. CONCLUSION: We have further characterized the FAT1 QTL on pig chromosome 4 and refined its map position considerably, from a QTL interval of 70 cM to a maximum region of 20 cM and a probable region as small as 3.3 cM. The flanking markers for the small region are RXRG and SDHC and the orthologous region of FAT1 in the human genome is located on HSA1q23.3 and harbors approximately 20 genes. Our strategy to further refine the map position of this major QTL will be i) to type new markers in our pigs that are recombinant in the QTL interval and ii) to perform Identity-By-Descent (IBD) mapping across breeds that have been strongly selected for lean growth.

Dataset Information

Refined mapping of a quantitative trait locus on chromosome 1 responsible for mouse embryonic death.

Publications

Refined mapping of a quantitative trait locus on chromosome 1 responsible for mouse embryonic death.

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