A missense mutation in solute carrier family 12, member 1 SLC12A1 causes hydrallantois in Japanese Black cattleReport as inadecuate

A missense mutation in solute carrier family 12, member 1 SLC12A1 causes hydrallantois in Japanese Black cattle - Download this document for free, or read online. Document in PDF available to download.

BMC Genomics

, 17:724

Non-human and non-rodent vertebrate genomics


BackgroundHydrallantois is the excessive accumulation of fluid within the allantoic cavity in pregnant animals and is associated with fetal mortality. Although the incidence of hydrallantois is very low in artificial insemination breeding programs in cattle, recently 38 cows with the phenotypic appearance of hydrallantois were reported in a local subpopulation of Japanese Black cattle. Of these, 33 were traced back to the same sire; however, both their parents were reported healthy, suggesting that hydrallantois is a recessive inherited disorder. To identify autozygous chromosome segments shared by individuals with hydrallantois and the causative mutation in Japanese Black cattle, we performed autozygosity mapping using single-nucleotide polymorphism SNP array and exome sequencing.

ResultsShared haplotypes of the affected fetuses spanned 3.52 Mb on bovine chromosome 10. Exome sequencing identified a SNP g.62382825G > A, p.Pro372Leu in exon 10 of solute carrier family 12, member 1 SLC12A1, the genotype of which was compatible with recessive inheritance. SLC12A1 serves as a reabsorption molecule of Na-K-2Cl in the apical membrane of the thick ascending limb of the loop of Henle in the kidney. We observed that the concentration of Na-Cl increased in allantoic fluid of homozygous SLC12A1 g.62382825G > A in a hydrallantois individual. In addition, SLC12A1-positive signals were localized at the apical membrane in the kidneys of unaffected fetuses, whereas they were absent from the apical membrane in the kidneys of affected fetuses. These results suggested that p.Pro372Leu affects the membrane localization of SLC12A1, and in turn, may impair its transporter activity. Surveillance of the risk-allele frequency revealed that the carriers were restricted to the local subpopulation of Japanese Black cattle. Moreover, we identified a founder individual that carried the mutation g.62382825G > A.

ConclusionsIn this study, we mapped the shared haplotypes of affected fetuses using autozygosity mapping and identified a de novo mutation in the SLC12A1 gene that was associated with hydrallantois in Japanese Black cattle. In kidneys of hydrallantois-affected fetuses, the mutation in SLC12A1 impaired the apical membrane localization of SLC12A1 and reabsorption of Na-K-2Cl in the thick ascending limb of the loop of Henle, leading to a defect in the concentration of urine via the countercurrent mechanism. Consequently, the affected fetuses exhibited polyuria that accumulated in the allantoic cavity. Surveillance of the risk-allele frequency indicated that carriers were not widespread throughout the Japanese Black cattle population. Moreover, we identified the founder individual, and thus could effectively manage the disorder in the population.

KeywordsHydrallantois hydrops allantois Solute carrier family 12, member 1 SLC12A1 Na-K-2Cl cotransporter NKCC2 Bartter syndrome Counter current mechanism Autosomal recessive disorder Autozygosity mapping Exome sequencing Japanese Black cattle AbbreviationsBTABos taurus chromosome

CNVCopy number variation

CRLCrown-rump length

PCRPolymerase chain reaction

SNPSingle nucleotide polymorphism

Electronic supplementary materialThe online version of this article doi:10.1186-s12864-016-3035-1 contains supplementary material, which is available to authorized users.

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Author: Shinji Sasaki - Kiyotoshi Hasegawa - Tomoko Higashi - Yutaka Suzuki - Sumio Sugano - Yasuaki Yasuda - Yoshikazu Sugimoto

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