RESUMO
The welfare of calves is important to both farmers and consumers. Practices that increase the proportion of calves born alive and enable them to thrive through to weaning contribute to improved sustainability. Stillbirths (SB) are calvings where the calf dies at birth or within 24 h after birth. Pre-weaning mortality (PWM) refers to calves that die after the first day of life but before weaning based on termination data. Both SB and PWM are binary traits characterized by low heritability. Data collection for these traits is incomplete, compared with traits like milk yield in cows. Despite these challenges, genetic variation can be measured and used to produce breeding tools, such as estimated breeding values (EBV), to reduce calf mortality over time. The aim of this study was to compare the performance of various linear models to predict SB and PWM traits in Holstein and Jersey cattle and evaluate their applicability for industry-wide use in the Australian dairy industry. Calving records from around 2.25 million Holstein and Jersey dams were obtained from DataGene's Central Data Repository from 2000 onwards to calculate genetic parameters. About 7% of calves were recorded as stillborn in the period 2000-2021 (n = 1.48 million calvings). The prevalence of PWM was much lower than stillbirth during the same period at 2% (n = 0.89 million calves). Genetic parameters were estimated for SB direct, SB maternal and PWM using bivariate linear models with calving ease (CE) as the second trait in the model. The heritability of these calf traits was low and varied between 1 to 5% depending on the breed, trait and model. In Holstein cattle, heritabilities were 2% for PWM and SB direct and 1% for SB maternal while in Jersey cattle heritabilities were 5% for PWM, 2% for SB direct and 1% for SB maternal. The genetic trends for both SB direct and maternal in Holstein cattle indicate improvement in both traits whereas there was no apparent increase or decrease in PWM in the past 2 decades. The coefficient of genetic variation for SB direct and PWM was between 11.7 and 23.0% in Holstein and Jersey cattle demonstrating that there was considerable genetic variation in calf survival traits as a first step to using genetic selection to increase the proportion of calves born alive and calves weaned. A focus on improved calf and calving recording practices is expected to increase the reliability of genetic predictions.
RESUMO
Germline mutations in genes encoding members of the transforming growth factor-ß (TGF-ß)/bone morphogenetic protein (BMP) superfamily are causal for two hereditary vascular disorders, hereditary hemorrhagic telangiectasia (HHT) and heritable pulmonary arterial hypertension (PAH). When the two diseases coexist, activin A receptor type II-like kinase-1 (ACVRL1) gene mutations are usually identified. We report a remarkable ACVRL1 germinal and somatic mosaicism characterized by the presence of two distinct mutant alleles and a non-mutant ACVRL1 allele in a woman diagnosed with PAH at the age 40. She also met the Curaçao diagnostic criteria for HHT based on additional findings of telangiectases, epistaxis and arteriovenous malformations. Mutation analysis of ACVRL1 identified two adjacent heterozygous deleterious mutations within exon 10: c.1388del (p.Gly463fsX2) and c.1390del (p.Leu464X) in a region enriched by mutation-associated DNA motifs. The mother transmitted the c.1388del to one child and the c.1390del to two children confirming germinal mosaicism. Allele-specific polymerase chain reaction analysis showed that c.1388del is the predominant mutation in lymphocytes of the index case. Haplotype analysis revealed that both mutant alleles have a common chromosomal origin which is distinct from that of the mother's non-mutant ACVRL1 allele. These distinct mutant alleles in tissues and germline could have arisen by DNA structure-mediated events occurring in the early stages of the mother's embryogenesis, prior to the segregation of her germline, which ultimately led to the independent transmission of each allele. These highlight the complexity of genomic events occurring during early embryogenesis and the consequences of mutational mosaicism upon pathogenic variability.
