Identification of small and large genomic candidate variants in bovine pulmonary hypoplasia and anasarca syndrome.

Häfliger, I. M.; Wiedemar, N.; Švara, T; Starič, J; Cociancich, V; Šest, K; Gombač, M; Paller, T; Agerholm, J S; Drögemüller, C. (2020). Identification of small and large genomic candidate variants in bovine pulmonary hypoplasia and anasarca syndrome. Animal genetics, 51(3), pp. 382-390. Wiley 10.1111/age.12923

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The pulmonary hypoplasia and anasarca syndrome (PHA) is a congenital lethal disorder, which until now has been reported in cattle and sheep. PHA is characterized by extensive subcutaneous fetal edema combined with hypoplasia or aplasia of the lungs and dysplasia of the lymphatic system. PHA is assumed to be of genetic etiology. This study presents the occurrence of PHA in two different cattle breeds and their genetic causation. Two PHA cases from one sire were observed in Slovenian Cika cattle. Under the assumption of monogenic inheritance, genome-wide homozygosity mapping scaled down the critical regions to 3% of the bovine genome including a 43.6 Mb-sized segment on chromosome 6. Whole-genome sequencing of one case, variant filtering against controls and genotyping of a larger cohort of Cika cattle led to the detection of a likely pathogenic protein-changing variant perfectly associated with the disease: a missense variant on chromosome 6 in ADAMTS3 (NM_001192797.1: c.1222C>T), which affects an evolutionary conserved residue (NP_001179726.1: p.(His408Tyr)). A single PHA case was found in Danish Holstein cattle and was whole-genome sequenced along with its parents. However, as there was no plausible private protein-changing variant, mining for structural variation revealed a likely pathogenic trisomy of the entire chromosome 20. The identified ADAMTS3 associated missense variant and the trisomy 20 are two different genetic causes, which shows a compelling genetic heterogeneity for bovine PHA.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Häfliger, Irene Monika; Wiedemar, Natalie and Drögemüller, Cord

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 590 Animals (Zoology)
600 Technology > 610 Medicine & health
600 Technology > 630 Agriculture

ISSN:

1365-2052

Publisher:

Wiley

Language:

English

Submitter:

Cord Drögemüller

Date Deposited:

26 Feb 2020 09:12

Last Modified:

10 May 2020 01:34

Publisher DOI:

10.1111/age.12923

PubMed ID:

32069517

Uncontrolled Keywords:

Mendelian cattle chromosomal aberration genetic disorder monogenic precision medicine rare disease trisomy

BORIS DOI:

10.7892/boris.140796

URI:

https://boris.unibe.ch/id/eprint/140796

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