Single-step genomic BLUP (ssGBLUP) effectively models small cattle populations: lessons from the Israeli-Holstein Herdbook.

Background: Routine genomic-estimated breeding values (gEBVs) are computed for the Israeli dairy cattle population by a two-step methodology in combination with the much larger Dutch population. Only sire genotypes are included. This work evaluated the contribution of cow genotypes obtained from the Israeli Holstein population to enhance gEBVs predictions via single-step genomic best-linear unbiased prediction (ssGBLUP).

A pathogenic variant in the uncharacterized gene results in severe aneuploidy male infertility and repeated IVF failure.

Quantitative and qualitative spermatogenic impairments are major causes of men's infertility. Although fertilization (IVF) is effective, some couples persistently fail to conceive. To identify causal variants in patients with severe male infertility factor and repeated IVF failures, we sequenced the exome of two consanguineous family members who underwent several failed IVF cycles and were diagnosed with low sperm count and motility.

Genetic and Genomic Analysis of Cow Mortality in the Israeli Holstein Population.

"Livability" was defined as the inverse of the probability of death. The objectives of this study were to estimate the heritability, genetic and phenotypic trends for the livability of Israeli Holstein cows; estimate the genetic and environmental correlations between livability and the nine traits included in the Israeli breeding index; estimate the effect of the inclusion of livability in the Israeli breeding index on expected genetic gains; and compute a genome-wide association study (GWAS) for livability. Seven data sets were analyzed.

Re-Evaluation of Genotyping Methodologies in Cattle: The Proficiency of Imputation.

In dairy cattle, identifying polymorphisms that contribute to complex economical traits such as residual feed intake (RFI) is challenging and demands accurate genotyping. In this study, we compared imputed genotypes ( = 192 cows) to those obtained using the TaqMan and high-resolution melting (HRM) methods ( = 114 cows), for mutations in the gene that had been suggested to have a large effect on RFI. Combining the whole genome sequence ( = 19 bulls) and the cows' BovineHD BeadChip allowed imputing genotypes for these mutations that were verified by Sanger sequencing, whereas, an error rate of 11.

Transgenerational transmission of environmental effects in livestock in the age of global warming.

Recent decades provide mounting evidence for the continual increase in global temperatures, now termed "global warming," to the point of drastic worldwide change in the climate. Climatic change is a long-term shift in temperatures and weather patterns, including increased frequency and intensity of extreme environmental events such as heat waves accompanied by extreme temperatures and high humidity. Climate change and global warming put several challenges to the livestock industry by directly affecting the animal's production, reproduction, health, and welfare.

Breeding Dairy Cattle for Female Fertility and Production in the Age of Genomics.

Phenotypic and genetic changes for female fertility and production traits in the Israeli Holstein population over the last three decades were studied in order to determine if long term selection has resulted in reduced heritability and negative genetic correlations. Annual means for conception status, defined as the inverse of the number of inseminations to conception in percent, decreased from 55.6 for cows born in 1983 to 46.

ExAgBov: A public database of annotated variations from hundreds of bovine whole-exome sequencing samples.

Large reference datasets of annotated genetic variations from genome-scale sequencing are essential for interpreting identified variants, their functional impact, and their possible contribution to diseases and traits. However, to date, no such database of annotated variation from broad cattle populations is publicly available. To overcome this gap and advance bovine NGS-driven variant discovery and interpretation, we obtained and analyzed raw data deposited in the SRA public repository.

Genetic and genomic analysis of age at first insemination in Israeli dairy cattle.

We performed a genetic analysis of age at first insemination, including estimation of the heritability and genetic correlations with other economic traits, and the consequences of including this trait in the Israeli selection index. The genetic factors affecting age at first insemination were determined via GWAS. Five data sets were analyzed.

Comparing BeadChip and WGS Genotyping: Non-Technical Failed Calling Is Attributable to Additional Variation within the Probe Target Sequence.

Microarray-based genomic selection is a central tool to increase the genetic gain of economically significant traits in dairy cattle. Yet, the effectivity of this tool is slightly limited, as estimates based on genotype data only partially explain the observed heritability. In the analysis of the genomes of 17 Israeli Holstein bulls, we compared genotyping accuracy between whole-genome sequencing (WGS) and microarray-based techniques.

Broad phenotypic impact of the effects of transgenerational heat stress in dairy cattle: a study of four consecutive generations.

Background: Global warming has increased the frequency of heat stress in livestock. Although heat stress directly leads to negative effects on production and reproduction traits in dairy cattle, the transgenerational transition of these changes is poorly understood. We hypothesized that heat stress in pregnant cows might induce epigenetic modifications in the developing embryo germ cells, which, in turn, might lead to phenotypic effects in the offspring.

Pathogenic variations in Germ Cell Nuclear Acidic Peptidase (GCNA) are associated with human male infertility.

Infertility affects one in six couples, half of which are caused by a male factor. Male infertility can be caused by both, qualitative and quantitative defects, leading to Oligo- astheno-terato-zoospermia (OAT; impairment in ejaculate sperm cell concentration, motility and morphology). Azoospermia defined as complete absence of sperm cells in the ejaculation.

Genetic and Genome-Wide Association Analysis of Yearling Weight Gain in Israel Holstein Dairy Calves.

Yearling weight gain in male and female Israeli Holstein calves, defined as 365 × ((weight - 35)/age at weight) + 35, was analyzed from 814,729 records on 368,255 animals from 740 herds recorded between 1994 and 2021. The variance components were calculated based on valid records from 2008 through 2017 for each sex separately and both sexes jointly by a single-trait individual animal model analysis, which accounted for repeat records on animals. The analysis model also included the square root, linear, and quadratic effects of age at weight.

Genetic and environmental analysis of female calf survival in the Israel Holstein cattle population.

The objectives were to estimate the effects of various environmental factors on female calf survival of Israeli Holsteins, to estimate the economic value of calf survival under Israeli conditions, to estimate the genetic and environmental variance components for calf and cow survival using the individual animal model, to perform GWAS analyses of survival to first calving and herd life after first calving, to estimate the genetic and environmental trends for calf survival since 1985, to estimate genetic correlations of calf survival with the traits included in the current Israeli breeding index, and to estimate the consequences of inclusion of calf survival in the national selection index. Mean calf survival rate of Israeli Holsteins from 2001 through 2008 was 0.85, and the mean economic value of survival to first calving was $526.

A Simplified and Efficient Method for Himar-1 Transposon Sequencing in Bacteria, Demonstrated by Creation and Analysis of a Saturated Transposon-Mutant Library in Mycobacterium abscessus.

We present a technically simple, easy-to-perform method for generating the genomic libraries for Himar-1 transposon site sequencing (Tn-seq). In addition to being simpler than present methods in the technical aspect, it also allows more robust and straightforward identification of the insertion site, by generating a longer sequence surrounding the insertion TA in the genome. The method makes Tn-seq more user-friendly and accessible to laboratories with more-limited bioinformatic resources.

Mutation in (C2orf62) causes oligoteratoasthenozoospermia by affecting actin dynamics.

Background: Oligoteratoasthenozoospermia (OTA) combines deteriorated quantity, morphology and motility of the sperm, resulting in male factor infertility.

Methods: We used whole genome genotyping and exome sequencing to identify the mutation causing OTA in four men in a consanguineous Bedouin family. We expressed the normal and mutated proteins tagged with c-Myc at the carboxy termini by transfection with pCDNA3.

Genetic and genomic analysis of long insemination interval in Israeli dairy cattle as an indicator of early abortions.

One of the causes of observed low fertility is embryo loss after fertilization. Previous findings suggested that more than half of fertilizations result in embryo loss before pregnancy is detected. We proposed reinsemination between 49 and 100 d after the first insemination as an indicator trait for early abortion (EA) in dairy cattle based on the mean estrus interval of 21 d.

Bos taurus-indicus hybridization correlates with intralocus sexual-conflict effects of PRDM9 on male and female fertility in Holstein cattle.

Background: Crossover localization during meiotic recombination is mediated by the fast-evolving zinc-finger (ZnF) domain of gene PRDM9. To study its impact on dairy cattle performance, we compared its genetic variation between the relatively small Israeli (IL) Holsteins and the North American (US) Holsteins that count millions.

Results: Initially, we analyzed the major BTA1 haplotypes present in IL Holsteins based on the 10 most telomeric SNPs of the BovineSNP50 BeadChip.

A new MEIOB mutation is a recurrent cause for azoospermia and testicular meiotic arrest.

Study Question: Are there genetic variants that can be used for the clinical evaluation of azoospermic men?

Summary Answer: A novel homozygous frame-shift mutation in the MEIOB gene was identified in three azoospermic patients from two different families.

What Is Known Already: Up to 1% of all men have complete absence of sperm in the semen, a condition known as azoospermia. There are very few tools for determining the etiology of azoospermia and the likelihood of sperm cells in the testis.

A cancer associated somatic mutation in LC3B attenuates its binding to E1-like ATG7 protein and subsequent lipidation.

Macroautophagy/autophagy is a conserved catabolic process that maintains cellular homeostasis under basal growth and stress conditions. In cancer, autophagy can either prevent or promote tumor growth, at early or advanced stages, respectively. We screened public databases to identify autophagy-related somatic mutations in cancer, using a computational approach to identify cancer mutational target sites, employing exact statistics.

A familial study of azoospermic men identifies three novel causative mutations in three new human azoospermia genes.

Purpose: Up to 1% of all men experience azoospermia, a condition of complete absence of sperm in the semen. The mechanisms and genes involved in spermatogenesis are mainly studied in model organisms, and their relevance to humans is unclear because human genetic studies are very scarce. Our objective was to uncover novel human mutations and genes causing azoospermia due to testicular meiotic maturation arrest.

The landscape of sex-differential transcriptome and its consequent selection in human adults.

Background: The prevalence of several human morbid phenotypes is sometimes much higher than intuitively expected. This can directly arise from the presence of two sexes, male and female, in one species. Men and women have almost identical genomes but are distinctly dimorphic, with dissimilar disease susceptibilities.

MalaCards: an amalgamated human disease compendium with diverse clinical and genetic annotation and structured search.

The MalaCards human disease database (http://www.malacards.org/) is an integrated compendium of annotated diseases mined from 68 data sources.

Absence of α- and β-dystroglycan is associated with Walker-Warburg syndrome.

Objective: To identify the underlying genetic defect in 5 patients from a consanguineous family with a Walker-Warburg phenotype, together with intracranial calcifications.

Methods: Homozygosity mapping and exome sequencing, followed by Sanger sequencing of the obtained candidate gene, was performed. Expression of the candidate gene was tested by reverse transcription PCR.

Disrupting mitochondrial-nuclear coevolution affects OXPHOS complex I integrity and impacts human health.

The mutation rate of the mitochondrial DNA (mtDNA), which is higher by an order of magnitude as compared with the nuclear genome, enforces tight mitonuclear coevolution to maintain mitochondrial activities. Interruption of such coevolution plays a role in interpopulation hybrid breakdown, speciation events, and disease susceptibility. Previously, we found an elevated amino acid replacement rate and positive selection in the nuclear DNA-encoded oxidative phosphorylation (OXPHOS) complex I subunit NDUFC2, a phenomenon important for the direct interaction of NDUFC2 with the mtDNA-encoded complex I subunit ND4.

Reduced selection and accumulation of deleterious mutations in genes exclusively expressed in men.

Sex-limited selection can moderate the elimination of deleterious mutations from the population and contribute to the high prevalence of common human diseases. Accordingly, deleterious mutations in autosomal genes that are exclusively expressed in only one of the sexes undergo sex-limited selection and can reach higher frequencies than mutations similarly selected in both sexes. Here we show that the number of deleterious SNPs in genes exclusively expressed in men is twofold higher than in genes that are selected in both sexes.