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At least 523 records · Page 29Linked to original sources
PubMed2004

Human controlled ovarian hyperstimulation outcome is a polygenic trait.

This study aimed to evaluate the association between follicle-stimulating hormone (FSH) hormone efficacy and FSHR, CYP19, ESR1 and ESR2 genes using single nucleotide polymorphism analyses. One hundred and seventy women with conserved ovarian function undergoing controlled ovarian stimulation (COS) with daily exogenous recombinant FSH administration. Women were categorized as poor responders to FSH (three or less ovarian follicles observed at the end of cycle) or normal responders (more than three follicles). The outcome is the number of normal/poor responders as defined by the number of follicles obtained during COS. The DNA markers studied are located in genes related to the FSH mechanism of action (FSH receptor, CYP19 aromatase and oestrogen receptors alpha and beta genes). We conducted an association study between the COS outcome and selected DNA markers using two-point and multi-locus genetic association studies. Genotype pattern tracking in extreme phenotypes and multi-locus analysis using Sumstat and PM algorithms provided significant evidences of genetic interaction between FSHR, ESR1 and ESR2 markers in relation to COS outcome (P = 0.0015). Our results support the hypothesis that a discrete set of genes, related to the FSH hormone mechanism of action, controls the ovarian response to FSH in humans. An oligogenic model including specific FSHR, ESR1 and ESR2 genotype patterns may partially explain the poor response to FSH hormone during controlled ovarian stimulation treatments. The existence of genetic heterogeneity is also suspected.

Adult↗
PubMed1993

Accounting for bias in estimates of the rate of polygenic mutation.

Experimental data on the rate of response to artificial selection in initially inbred lines or the rate of divergence among inbred sublines can be used to estimate the rate of increase in variance of quantitative traits from new mutations. So far estimates have been based on the infinitesimal model of many genes with small additive effects which imply a rate of increase in heritability for Drosophila melanogaster bristle number traits of about 0.1% per generation. Such estimates are biased because mutants tend to have large effects, to have non-additive gene action, and to be deleterious. Here, recent information on the distribution of effects of new mutations on Drosophila melanogaster bristle number and viability is used to infer the direction and magnitude of this bias. The infinitesimal model tends to underestimate the mutational variance, typically by a factor of about 3, but this factor depends on the experimental design. Averages of revised estimates, accounting for this bias, of the per generation increment in heritability from mutation are 0.36% and 0.21% for abdominal and sternopleural bristle number, respectively, in experiments involving M strains, and 1.4% and 0.7% for abdominals and sternopleurals, respectively, in P strains.

Animals↗
PubMed1977

Polygenic control of mixed lymphocyte reaction in dogs.

The genetics of the MLR of the dog are studied using LD typing cells. The four new homozygous reference cells described bring the total number of defined LD specificities in this species to 11. In families, LD specificities generally segregate en block with the SD specificities of the DLA complex. The recombination frequency between the SD and LD loci is provisionally estimated to be 0.007. A slight but significant stimulation between two SD identical LD typed siblings could not be explained on the basis of a single recombination between the SD loci and one LD locus and therefore suggested the existence of an additional LD system. Unrelated SD different individuals with two different LD determinants in common frequently stimulate each other in MLR, but low responses are also encountered. The results described are compatible with a hypothesis of two segregant series of alleles for the genetic control of the MLR and linkage disequilibrium between certain alleles of these series. More conclusive evidence of the validity of this hypothesis and further knowledge of other factors which determine the response in the MLR are required before a reliable estimate of the importance of LD structures in histocompatibility can be made.

Animals↗
PubMed1988

Effects of environmental changes on the phenotypic expression of human polygenic traits.

The very large increase in adult stature during the last century is well documented for many countries and this phenomenon has been associated with the rapid improvement of environmental conditions. In the case of Italy, data relative to its regions and drawn from the military records of the last century showed a rapid normalization (i.e. elimination of both negative skewness and hyperkurtosis) of the distribution (1874-1938), followed by acceleration of the average increase (1938-57), which is now approaching a plateau (1957-64). Two different interactions between genotype and environment are hypothesized: the curve normalization is interpreted as being due to the elimination of extremely unfavourable conditions which inhibit growth, while the rapid stature increase is possibly due to the achievement of an environmental threshold, such as to permit a complete expression of the genetic potential. In fact, under the multifactorial model, a perfectly normal distribution is expected, unless there is differential selection before age 18.

Adolescent↗
PubMedDate not supplied

The contribution of epistatic pleiotropy to the genetic architecture of covariation among polygenic traits in mice.

The contribution that pleiotropic effects of individual loci make to covariation among traits is well understood theoretically and is becoming well documented empirically. However, little is known about the role of epistasis in determining patterns of covariation among traits. To address this problem we combine a quantitative trait locus (QTL) analysis with a two-locus model to assess the contribution of epistasis to the genetic architecture of variation and covariation of organ weights and limb bone lengths in a backcross population of mice created from the M16i and CAST/Ei strains. Significant epistasis was exhibited by 14 pairwise combinations of QTL for organ weights and 10 combinations of QTL for limb bone lengths, which contributed, on average, about 5% of the variation in organ weights and 8% in limb bone lengths beyond that of single-locus QTL effects. Epistatic pleiotropy was much more common in the limb bones (seven of 10 epistatic combinations affecting limb bone lengths were pleiotropic) than the organs (three of the 14 epistatic combinations affecting organ weights were pleiotropic). In both cases, epistatic pleiotropy was less common than single-locus pleiotropy. Epistatic pleiotropy accounted for an average of 6% of covariation among organ weights and 21% of covariation among limb bone lengths, which represented an average of one-fifth (for organ weights) and one-third (for limb bone lengths) of the total genetic covariance between traits. Thus, although epistatic pleiotropy made a smaller contribution than single-locus pleiotropy, it clearly made a significant contribution to the genetic architecture of variation/covariation.

Animals↗
PubMed1992

Polygenic influences on the length of oestrous cycles in inbred mice involve MHC alleles.

Genetic influences on female reproductive cycles were analysed in histocompatibility-congenic strains of mice. Oestrous cycles of young, virgin mice of inbred-congenic strains, hybrid crosses (F1), and parental-hybrid backcrosses (F2) were monitored for 3 months. Oestrous cycles were categorized by length (inter-oestrous interval): 4, 5, 6, or 7-14 days. Mice with the following H-2 haplotypes had a greater proportion of 5-day oestrous cycles: H-2b, H-2r, H-2h2, H-2h4, and H-2i5. In contrast, the H-2k and H-2d haplotypes had mostly 4-day oestrous cycles. Influences of H-2 haplotype were seen on two genetic backgrounds, C57BL/10Sn and C3H. Non-H-2 alleles were also implied by different patterns of cycles between strains with the same H-2b haplotype: C57BL/10Sn with predominantly 5-day cycles vs. C57BL/6J with a mix of 4- and 5-day cycles. The genetic basis for strain differences was investigation in F1 hybrids and their backcrosses. F1 hybrids of an H-2b (C57BL/10Sn; 5-day cycles) and an H-2k (B10.BR; 4-day cycles) strain had mostly 5-day cycles, indicating dominance of an H-2b allele(s). However, F1 hybrids from the reciprocal B6 x B10 cross (both H-2b) also display a preponderance of 5-day cycles, indicating dominance of a non-H-2 autosomal allele from the C57BL/10Sn strain. Among F2 mice, a '4-day' phenotype segregated with homozygosity for the k haplotype (P < 0.05, chi 2). These findings demonstrate the influence of genetic differences at the major histocompatibility complex on oestrous cycles.

Alleles↗
PubMed1996

Polygenic determinants of Alzheimer's disease: modulation of the risk by alpha-1-antichymotrypsin.

The identification of apolipoprotein E (APOE) as a genetic risk factor modifying the chances of developing Alzheimer's disease (AD) has opened the possibility that other susceptibility genes exist that either independently modify the risk of developing AD or alter the risk imparted by APOE. We have identified alpha-1-antichymotrypsin (ACT) as a potential risk gene, by virtue of the interactive effect of either of its two alleles (A and T) on the risk of AD associated with the APOE epsilon 4 allele. In a large population of AD (n = 308) and control (n = 579) cohorts, we found the expected elevation in the APOE epsilon 4 allele frequency in the AD cases compared to controls, with threefold and sevenfold increases in the risk of AD for APOE epsilon 4/X and APOE epsilon 4/epsilon 4, respectively. Of the three ACT genotypes, the ACT A/T genotype did not affect the risk of AD beyond that which is conferred by the APOE epsilon 4 allele. However, the ACT A/A genotype greatly increased the risk associated with APOE epsilon 4 homozygosity. On the other hand, the ACT T/T genotype suppressed the gene dosage effect of the APOE epsilon 4 allele; the risk of AD in APOE epsilon 4/epsilon 4, ACT T/T cases was the same as that of APOE epsilon 4/X. A variety of potential mechanisms for interactions of ACT and APOE are discussed.

Adult↗
PubMed2025

Evolutionary legacy of the "living fossil" genus Parrotia (Hamamelidaceae): genomic insights into species divergence and polygenic adaptation.

Despite their long evolutionary history, the genomic basis of adaptation and speciation in "living fossil" plants remain largely unexplored. Parrotia, a Tertiary relict tree genus with two extant species, P. subaequalis and P. persica, exhibits a disjunct distribution between East Asia and West Asia. Here, we present the first chromosome-level assemblies for both species, confirmed their sibling relationship, and dated the speciation event to the early Miocene. The recent proliferation of long-terminal repeat retrotransposons has driven the genome expansion in P. subaequalis. We detected widespread heterogeneous genomic differentiation between species. Extensive signals of divergent selection, local adaptation, and elevated Ka/Ks ratios in Parrotia indicate that this genus has undergone adaptive evolution in distinct refugia, challenging the notion of it as an "evolutionary dead end". Our findings provide new insights into the genomic evolution, environmental adaptation, and speciation of this "living fossil" tree genus.

Genome, Plant↗
PubMed1986

Virulence of La Crosse virus is under polygenic control.

To identify which RNA segments of the California serogroup bunyaviruses determine virulence, we prepared reassortant viruses by coinfecting BHK-21 cells with two wild-type parents, La Crosse/original and Tahyna/181-57 viruses, which differed about 30,000-fold in virulence. The progeny clones were screened by polyacrylamide gel electrophoresis to ascertain the phenotype of the M and S RNA segments, and RNA-RNA hybridization was used to determine the genotype of selected clones. Two or three clones of each of the six possible reassortant genotypes were characterized quantitatively for neuroinvasiveness by determining the PFU/50% lethal dose (LD50) ratio after subcutaneous injection into suckling mice. The reassortants fell into two groups. (i) Six of seven reassortants with a La Crosse M RNA segment were as virulent as the parent La Crosse virus (about 1 PFU/LD50); the one exception was strikingly different (about 1,000 PFU/LD50) and probably represents a spontaneous mutant. (ii) The seven reassortants with a Tahyna M RNA segment were about 10-fold more virulent than the parent Tahyna virus (median 1,600 PFU/LD50 for reassortants and 16,000 PFU/LD50 for Tahyna virus). A comparative pathogenesis study in suckling mice of one reassortant virus and the parent Tahyna virus confirmed the greater neuroinvasiveness of the reassortant virus. From these data it was concluded that the M RNA segment was the major determinant of virulence, but that the other two gene segments could modulate the virulence of a nonneuroinvasive California serogroup virus.

Animals↗
PubMed1993

Polygenic control of neuroinvasiveness in California serogroup bunyaviruses.

The pathogenesis of the California serogroup bunyaviruses includes both extraneural and intraneural replicative phases that can be separated experimentally. The present study dissects the viral genetic determinants of extraneural replication. We have previously described two attenuated reassortant clones of California serogroup bunyaviruses which exhibit reduced neuroinvasiveness after subcutaneous inoculation into suckling mice. Clone B1-1a bears an attenuated middle RNA segment (neuroinvasiveness phenotype v alpha v), and clone B.5 bears an attenuated large RNA segment (neuroinvasiveness phenotype alpha vv). We prepared reassortant viruses between these two strains and found that the two attenuated gene segments acted independently and additively, since reassortants bearing two attenuated RNA segments were more attenuated than the parental clones. Reassortants bearing no attenuated RNA segments were much more neuroinvasive than either parental clone, indicating that a neuroinvasive strain can be derived from two attenuated clones. Pathogenesis studies demonstrated that after injection of 10(3) PFU, the attenuated reassortant clones did not replicate in peripheral tissue, failed to reach the brain, and did not cause disease. At a dose of 10(6) PFU, attenuated clones failed to replicate to a significant level in peripheral tissue and produced only a minimal passive plasma viremia during the first 24 h but nevertheless reached high titers in the brain and killed mice. Because of this result, we investigated the possibility that neuroinvasion occurs via retrograde axonal transport, by determining whether sciatic nerve sectioning could protect against virus infection after hind leg footpad inoculation. We found that nerve sectioning had no effect on lethality, ruling out this mode of entry and suggesting that passive viremia is likely to be sufficient for invasion of the central nervous system.

Animals↗