The impact of Fishers Reproductive Compensation on raising equilibrium frequencies of semi-dominant, non-lethal mutations under mutation/selection balance.

Fishers reproductive compensation (fRC) occurs when a species demography means the death of an individual allows increased survival of his/her relatives, usually assumed to be full sibs. This likely occurs in many species, including humans. Several important recessive human genetic diseases cause early foetal/infant death allowing fRC to act on these mutations. The impact of fRC on these genetic conditions has been calculated and shown to be substantial as quantified by w, the fold increase in equilibrium frequencies of the mutation under fRC compared to its absence i.e. w=1.22 and w =1.33 for autosomal and sex-linked loci, respectively. However, the impact of fRC on the frequency of the much large class of semi-dominant, non-lethal mutations is unknown. This is calculated here by a mixture of simulation and algebra and shown that w is approximately 2-h*s and 2-0.19s-0.85h*s for autosomal and sex-linked loci respectively where h is dominance (varied between 0.05 and 0.95) and s is selection coefficient (varied between 0.05 and 0.9). These results show that the actions of fRC can almost double equilibrium frequency of mutations with low values of h and/or s. The dynamics of fRC acting on this type of mutation are also identified and discussed.

Influence of inbreeding on the morphobiological characteristics of meadow clover (Trifolium pratense L.)

The influence of inbreeding on the morphobiological characteristics of meadow clover was revealed. Self-pollination, repeated in the number of successive generations, leads to an increase in homozygosity and to inbred depression, which increases from I1 to I3 generation and stabilizes in the I4 generation. It was found that in the I1 generation, according to the main morphobiological characteristics, there is no inward depression, but the maximum release of recessive lethal mutations is manifested, which amounted to 6.2%, and the survival rate of seedlings decreases (91.7%). By the I4 generation, the number of chlorophyll-free seedlings decreases to 1.4%. All the main morpho-biological indicators that determine the productivity of plants decrease from generation I1 to generation I3 by 1.5-2 times and stabilize in generation I4. Obtaining hybrid F1 offspring by crossing a linear material with an I4 induction level leads to the restoration of plant productivity indicators. When creating a linear material, an increase in the number of highly self-compatible genotypes from I1 to I4 generation by 60% is clearly traced. The data obtained make it possible to take into account the survival rate of seedlings, the cleavage of lethal and semi-lethal mutations, the degree of inbred depression in the formation of sample volumes when creating a linear material of meadow clover.

Inbreeding effects in Drosophila congenic strains: the influence of genetic background of different origin

Aim. To compare reproductive indices and stress resistance of Drosophila at outbreeding and inbreeding. Methods. Drosophila melanogaster congenic strains with incomplete development of the radial wing vein – radius incompletus – were used: the laboratory one and the strain, in which the mutation was placed into the genetic background of wild type strain, which originates from the natural population from radiation contaminated territory. Before the experiment strains have passed 65 generations of inbreeding. Viability (number of individuals, pupa stage mortality), dominant lethal mutations frequency and life span of imago at starvation were analysed. Results. After inbreeding, there was a decrease in the frequency of dominant lethal mutations and an increase in viability of the strain, which originates from the natural population, and a decrease of mortality at the pupal stage in both strains. Decreased life span of imago at starvation has been shown only for the inbred strain, which originates from the natural population. Conclusions. Inbreeding for 65 generations has no significant negative effect on reproductive indices; reduction of stress resistance during inbreeding has been shown only for the strain, which originates from the radiation contaminated territory. Keywords: Drosophila, viability, dominant lethal mutations, life span of imago at starvation, inbreeding.

Identification of homozygous haplotypes carrying putative recessive lethal mutations that compromise fertility traits in French Lacaune dairy sheep

Background Homozygous recessive deleterious mutations can cause embryo/fetal or neonatal lethality, or genetic defects that affect female fertility and animal welfare. In livestock populations under selection, the frequency of such lethal mutations may increase due to inbreeding, genetic drift, and/or the positive pleiotropic effects of heterozygous carriers on selected traits. Results By scanning the genome of 19,102 Lacaune sheep using 50 k single nucleotide polymorphism (SNP) phased genotypes and pedigree data, we identified 11 Lacaune deficient homozygous haplotypes (LDHH1 to LDHH11) showing a highly significant deficit of homozygous animals ranging from 79 to 100%. These haplotypes located on chromosomes 3, 4, 13, 17 and 18, spanned regions from 1.2 to 3.0 Mb long with a frequency of heterozygous carriers between 3.7 and 12.1%. When we compared at-risk matings (between carrier rams and daughters of carrier rams) and safe matings, seven of the 11 haplotypes were associated with a significant alteration of two fertility traits, a reduced success of artificial insemination (LDHH1, 2, 8 and 9), and/or an increased stillbirth rate (LDHH3, 6, 8, 9, and 10). The 11 haplotypes were also tested for a putative selective advantage of heterozygous carrier rams based on their daughter yield deviation for six dairy traits (milk, fat and protein yields, fat and protein contents and lactation somatic cell score). LDHH1, 3, 4, 5, 7, 9 and 11 were associated with positive effects on at least one selected dairy trait, in particular milk yield. For each haplotype, the most probable candidate genes were identified based on their roles in lethality of mouse knock-out models and in mammalian genetic disorders. Conclusions Based on a reverse genetic strategy, we identified at least 11 haplotypes with homozygous deficiency segregating in French Lacaune dairy sheep. This strategy represents a first tool to limit at-risk matings in the Lacaune dairy selection scheme. We assume that most of the identified LDHH are in strong linkage disequilibrium with a recessive lethal mutation that affects embryonic or juvenile survival in sheep but is yet to be identified.

Antimutagenic activity of probiotic drugs on the example of Drosophila

Probiotic preparations were obtained on the basis of cryopreserved forms of pure cultures of L. plantarum and B. subtilis using freeze drying. The antimutagenic activity of the obtained probiotic preparations was investigated in relation to 1%, 0.1% and 0.01% concentrations of cobalt sulfate using the example of dominant lethal mutations of Drosophila. A positive antimutagenic effect of probiotic preparations was shown in relation to 0.1% and 0.01% concentrations of CoSO4 with an exposure duration of at least 3 days.

Lethal and semi-lethal mutations in Holstein calves in Uruguay

ABSTRACT: Genetic disorders in Holstein cattle are a health problem that has grown worldwide in recent years, compromising the sustainability of modern dairy production. In Uruguay, Holstein-based milk production is one of the most important sectors of the country’s economy, but high levels of inbreeding have decreased the breed’s fertility in recent decades. This study investigated the presence and diffusion of lethal and semi-lethal alleles causing embryo death, abortions, fetal malformations, and neonatal diseases in Holstein calves. Using the GeneSeek® Genomic Profiler™ Bovine 50K BeadChip, we genotyped 383 calves (1-30 days-old) from 27 farms located in the main dairy region of Uruguay. Results showed a high prevalence of farms (85%) and carrier calves (21%), including one or more of the following semi-lethal or lethal alleles: Syndactylism (4.18%), brachyspina (3.39%), cholesterol deficiency haplotype (2.61%), complex vertebral malformation (2.09%), bovine leukocyte adhesion deficiency (1.04%s), and Holstein haplotypes HH1 (4.44%), HH3 (3.13%), HH4 (1.04%), and HH5 (0.26%). Most of these alleles had not been recognized previously in Uruguay. We concluded that lethal and semi-lethal mutations are widespread in the Holstein breed in Uruguay. More studies are required to determine their impact on dairy cattle fertility.