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More on red blood cell genetic variation in Olympic athletes.

As a follow-up to De Garay et al. (1976) and Chagnon et al. (1984) studies, we are reporting on the genetic variation of four red blood cell enzymes in 49 athletes with isoelectric-focusing and electrophoresis techniques. The athletes were Caucasians participating in the 1976 Montreal Olympic Games. They were performing in 5 different sports and the sample included 18 women and 31 men. No uncommon allele was found and all known alleles were detected for each enzyme. Phenotypes and gene frequencies were computed and compared with appropriate populations of reference. No significant differences were observed for any of the enzymes. Moreover, no association was found between variation in these proteins and participation in rowing (N = 25) or track (N = 13) event.

Acid Phosphatase↗

Genetic variation in Brac, Croatia.

A serological survey of the Dalmatian island of Brac (Croatia), based on a total sample of 747 subjects, shows considerable local genetic variation. While the overall gene frequencies are much as expected from the island's geographical position, the local genetic heterogeneity is made up of differences between the inland and coastal villages, differences between the two coastal areas, and variation among the older inland villages. This heterogeneity is interpreted as deriving from the settlement process (founder effect), random differentiation, and the essentially local marriage pattern.

Blood Group Antigens↗

Genetic variation in alpha 2HS-glycoprotein is related to calcaneal broadband ultrasound attenuation in older women.

Calcaneal broadband ultrasound attenuation (BUA) is an independent predictor of hip and vertebral fractures. BUA is under genetic control, but the specific genes contributing to BUA are not well defined. We examined the relationship between genetic variation in alpha2HS-glycoprotein (AHSG), an abundant noncollagenous protein of bone matrix, and calcaneal BUA. Genetic polymorphism in AHSG was determined in 222 Caucasian women (age 66-92) enrolled in the Pittsburgh Study of Osteoporotic Fractures clinical center by isoelectric focusing of serum samples. Calcaneal BUA and bone mineral density (BMD) were measured on the same foot with a Walker Sonix UBA 575(+) and single X-ray absorptiometry. Hip and spine BMD were determined with a Hologic QDR-1000 densitometer using dual-energy X-ray absorptiometry. AHSG polymorphism was not significantly related to hip, lumbar spine, or calcaneal BMD. Compared with the homozygous AHSG*2 women, calcaneal BUA was 13% lower in heterozygous (P < 0.05) and 16% lower in homozygous AHSG*1 women (P < 0.05). This relationship persisted after controlling for age, weight, height, walks for exercise, and calcaneal BMD. Current and self-reported height were also lowest in homozygous AHSG*1 women, intermediate in heterozygous women, and highest among homozygous AHSG*2 subjects. These results suggest that the AHSG polymorphism may contribute to the genetic influence on calcaneal BUA and stature.

Aged↗

Genetic variation in Echinacea angustifolia along a climatic gradient.

BACKGROUNDS AND AIMS: Echinacea angustifolia is a widespread species distributed throughout the Great Plains region of North America. Genetic differentiation among populations was investigated along a 1500 km north-south climatic gradient in North America, a region with no major geographical barriers. The objective of the study was to determine if genetic differentiation of populations could be explained by an isolation-by-distance model or by associations with climatic parameters known to affect plant growth and survival. METHODS: Historical climatic data were used to define the nature of the climatic gradient and AFLP markers were used to establish patterns of population genetic differentiation among ten Echinacea populations collected from North Dakota to Oklahoma. A total of 1290 fragments were scored using six EcoRI/MseI and three PstI/MseI primer combinations. Assessment of the correlation between climatic, genetic and geographic distances was assessed by Mantel and partial Mantel tests. KEY RESULTS: PstI/MseI combinations produced significantly fewer fragments, but a larger percentage was unique compared with EcoRI/MseI markers. Using estimates of F(ST), populations in Oklahoma and southern Kansas were identified as the most divergent from the other populations. Both the neighbour-joining tree and principal co-ordinate analysis clustered the populations in a north-south spatial orientation. About 60% of the genetic variation was found within populations, 20% among populations and the remaining 20% was partitioned among groups that were defined by the topology of the neighbour-joining tree. Significant support was found for the isolation-by-distance model independent of the effects of annual mean precipitation, but not from annual mean temperature and freeze-free days. CONCLUSIONS: Echinacea angustifolia populations exhibit genetic divergence along a north-south climatic gradient. The data support an isolation-by-distance restriction in gene flow that is independent of annual mean precipitation.

Adaptation, Physiological↗

[Analysis of genetic variation in rare endemic species Oxytropis chankaensis Jurtz. (Fabaceae) using RAPD markers].

The method of polymerase chain reaction with random primers (RAPD) was used to assess genetic variation and population differentiation in the rare endemic plant Oxytropis chankaensis Jurtz. (Fabaceae). DNA samples from plants of two isolated populations were compared at 133 loci detected by use of ten primers. Both populations examined were characterized by high polymorphism levels (P95 = 72.9%, A = 1.92 and P95 = 74.4%, A = 1.88, respectively). They were also statistically significantly different in the frequencies of most of the amplicons. For each of the plants, unique multilocus RAPD phenotype was established using 17 to 20 RAPD markers. Diagnostic markers were not revealed. The populations were poorly differentiated. On average, the between-population component accounted for about 8% of the variation, while 92% of the variation was detected within populations. High variation along with the low degree of differentiation characteristic of two most geographically remote populations of O. chankaensis can have several explanations, among which a polyploid origin of the species seems to be most important.

DNA Primers↗

Tissue-specific genetic variation in the level of mouse alcohol dehydrogenase is controlled transcriptionally in kidney and posttranscriptionally in liver.

Tissue-specific genetic variation in expression of the alcohol dehydrogenase, encoded by the Adh-1 gene, is found between C57BL/6J (B6) mice and B6.S congenic mice. B6.S mice contain a variant Adh-1 allele derived from a wild Danish strain in a B6 genetic background. B6 mice have nearly twice the alcohol dehydrogenase activity in liver but less than half the activity in kidney as B6.S mice. These tissue-specific genetic changes in alcohol dehydrogenase expression are manifest at the level of Adh-1-encoded mRNA. The regulatory site(s) involved act cis in both kidney and liver. These strains also differ in the extent to which androgen induces mRNA encoded by kidney Adh-1, with androgen increasing these levels 17-fold and 7.4-fold in the B6 and B6.S kidney, respectively. To identify the regulatory mechanism(s) underlying this strain variation in Adh-1 transcription in the B6 and B6.S kidney, liver, and androgen-induced kidney. For both uninduced and induced kidney, a difference in the transcription rate alone accounts for the strain difference in mRNA concentration. In contrast, because the Adh-1 transcription rate in liver does not differ significantly between B6 and B6.S mice, strain-specific variation in posttranscriptional regulation must be operative. Taken together these results indicate that the variation in Adh-1 expression between B6 and B6.S mice results from changes in both transcriptional and posttranscriptional control, and these controls are differentially operative in kidney and liver.

Alcohol Dehydrogenase↗

Case-control study and transmission disequilibrium test provide consistent evidence for association between schizophrenia and genetic variation in the 22q11 gene ZDHHC8.

Genetic variants in the 22q11 gene ZDHHC8, which encodes a putative transmembrane palmitoyltransferase, has been associated to schizophrenia in family-based linkage disequilibrium (LD) studies. The single nucleotide polymorphism (SNP) rs175174 (A/G), which had the strongest association, has been shown recently to regulate the level of the fully functional transcript by modulating the retention of intron 4 of ZDHHC8. In this work, we genotyped three genetic variants within the ZDHHC8 locus and conducted association studies in both population- and family-based samples of the Han Chinese population. The three polymorphisms spanning approximately 5.5 Kb were detected to be in significant LD. Our results provided compelling supportive evidence for association of the variants within the ZDHHC8 locus with schizophrenia but revealed different risk allele at SNP rs175174. The G allele was significantly more common in cases than in controls (69.47 : 59.96%; P=0.000018) and excess transmission of the same allele was confirmed in the family-based transmission disequilibrium test (transmitted/non-transmitted=87 : 54; P=0.0055). Both sample sets even shared the same risk haplotype with similar frequency. Our current data presents consistent association results obtained from both case-control and family-based samples in a same laboratory under the same experimental condition. Despite the potential genetic heterogeneity, our independent findings further support that the 22q11 region is likely to harbor candidate schizophrenia susceptibility genes.

Acyltransferases↗

Genetic variation and joint segregation of biochemical loci in the common meadow mushroom, Agaricus campestris.

In this paper we report the results of an electrophoretic examination of genetic variation in the common meadow mushroom, Agaricus campestris. An examination of variability at 10 biochemical loci in a single natural population revealed an average heterozygosity of 0.281. Mendelian segregation was verified for 13 loci in single-spore-derived lines from individual sporophores. One linkage was found (Gpt-2 with Pep-GL-1, r = 0.065) among 47 pairwise examinations for joint segregation.

Basidiomycota↗

Genetic variation and relationships of constitutive and herbivore-induced glucosinolates, trypsin inhibitors, and herbivore resistance in Brassica rapa.

We examined genetic variation in inducibility and in constitutive and herbivore-induced levels of glucosinolates, trypsin inhibitors, and resistance to herbivory in families of Brassica rapa originating from a wild population. We also examined phenotypic and genetic correlations among absolute levels of these traits in control and induced plants. We grew seedlings of 10 half-sib families in pairs in pots, and exposed one plant per pair to folivory by Trichoplusia ni larvae. Two days later, we sampled all plants for total glucosinolate and trypsin inhibitor levels and examined the preference and consumption by T. ni larvae of previously damaged (induced) and undamaged (control) plants. There was no significant variation among sire families in the induction of glucosinolates or trypsin inhibitors by T. ni feeding. Total glucosinolate levels in either control or induced plants did not vary by family. In contrast, trypsin inhibitor levels in both control and induced plants varied significantly by family. Trichoplusia ni fed less on induced plants than on control plants in the bioassay, but neither the induction of resistance by prior T. ni feeding nor absolute levels of damage done to control and induced plants varied significantly by sire family. Temporal blocking strongly affected trypsin inhibitor levels and the response of some families in the bioassays. There were no significant phenotypic or genetic correlations of levels of glucosinolates or trypsin inhibitors with each other or with damage in either control or induced plants. Overall, these results suggest that in the B. rapa population that we studied, both total glucosinolate content and biological resistance to herbivory by T. ni was nonvariable and almost universally inducible by prior T. ni feeding. In contrast, control and induced levels of trypsin inhibitors varied genetically and have the capacity to respond to future selection imposed by herbivores. However, the role of these defenses in constitutive or induced resistance to T. ni in this species remains unclear.

Adaptation, Physiological↗

Possible genetic variation in resistance of turkeys to erysipelas and fowl cholera.

Natural disease outbreaks of erysipelas and fowl cholera occurred in several lines of turkeys maintained for genetic studies. There were line differences in mortality during both outbreaks, suggesting that there is genetic variation in resistance to these diseases. A line developed by selection for increased egg production had a higher mortality rate from fowl cholera than did the randombred control line from which it was developed. Both the egg line and its control line had a lower mortality rate in the erysipelas outbreak than did a line selected for increased growth rate. Both diseases induced high mortality in a line selected for increased growth.

Animals↗

Genetic architecture of postpartum psychosis: from common to rare genetic variation.

Postpartum psychosis is a severe psychiatric condition marked by the abrupt onset of psychosis, mania, or psychotic depression following childbirth. Despite evidence for a strong genetic basis, the roles of common and rare genetic variation remain poorly understood. Leveraging data from Swedish national registers and genomic data from the All of Us Research Program, we estimated family-based heritability at 55% and whole-genome sequencing-based heritability at 46%. Rare coding variant analysis identified HMGCR as a gene in which rare damaging variants confer risk for postpartum psychosis (FDR&#x2009;<&#x2009;0.05). Analyses of 240,009 participants from the All of Us Research Program and 58,990 participants from the Mount Sinai BioMe Biobank identified significant associations linking deleterious rare variants in HMGCR to vascular dementia and mental disorder, not otherwise specified, supporting the gene's broader psychiatric relevance. Additionally, among the top 200 genes ranked by association statistics, 17% of bipolar disorder, 21% of schizophrenia, and 16-25% of multiple autoimmune disorders exhibit a possible association with postpartum psychosis. These findings reveal unique genetic contributions and shared pathways, providing a foundation for understanding pathophysiology and advancing therapeutic strategies.

Humans↗

[Study on the genetic variations of the major neutralization antigen VP7 of group A rotavirus type G1 in China].

OBJECTIVE: To study the genetic variations of the major neutralization antigen VP7 of group A rotavirus, type G1 in China. METHODS: Twenty-three isolates derived from seven cities (Beijing, Shenyang, Xinxiang, Shanghai, Shenzhen, Guangzhou and Chongqing) during the period of 1988-1998 were analyzed for the VP7 cDNA sequences. RESULTS: An obvious homology was observed in amino acid sequences of VP7 in the 23 isolates. Compared with the standard strain Wa, the variations were found at the position of aa 41, 49, 57, 65, 68, 74, 94, 97, 147, 170, 217, 218, 268, 281 and 291, respectively, and all of these were located in the variable region(VR)3,4,5,7,8 as well as in the C-terminal of the peptide. There seemed to be no remarkable divergence among the samples collected from different cities and all of them shared the same genetic lineage with the strain Jpn-417, though there might be one or two amino acid substitutions as time passed. When detected simultaneously with ELISA using G1 serotype-specific monoclonal antibody, the location of amino acid 91 was found presumably related to the neutralization epitope in VP7 of the type G1. Variations at some position may be resulted in the change of electropherotype. CONCLUSIONS: The results indicated that the recent isolates with representative genetic and antigenic features should be used to develop effective vaccines, and the antigenic variations should be monitored periodically.

Amino Acid Sequence↗

Genetic variation in the corticotrophin-releasing factor receptors: identification of single-nucleotide polymorphisms and association studies with obesity in UK Caucasians.

OBJECTIVE: To investigate whether genetic variation at the loci encoding the corticotropin-releasing factor receptors-1 and -2 (CRF-R1 and CRF-R2) contributes to human obesity. DESIGN: The coding region of the CRF-R1 and CRF-R2 genes was screened in 51 severely obese children (body mass index (BMI)>4 kg/m(2) standard deviations above the age-related mean) using denaturing high-performance liquid chromatography and direct nucleotide sequencing. Common polymorphisms that were identified were typed from a UK Caucasian population-based cohort by a PCR-based forced restriction digestion. A repeated measures analysis was used to determine associations between the C861T and G1047A genotypes and anthropometric and biochemical indices relevant to obesity. RESULTS: In subjects with extreme early-onset obesity, four missense mutations were found, each in a single individual: CRF-R1 (Val161Met) and CRF-R2 (Glu220Asp, Val240Ile and Val411Met). However, none of these missense mutations clearly cosegregated with obesity in family studies. Two common single-nucleotide polymorphisms, C861T (Cys287Cys) in CRF-R1 and G1047A (Ser349Ser) in CRF-R2, were also detected. G1047A did not associate with any obesity-related phenotype. In contrast, carriers of the CRF-R1 polymorphism, C861T, had a significantly higher body mass index (BMI). CONCLUSION: Mutations in the coding sequence of the CRF-R1 and CRF-R2 genes are unlikely to be a common monogenic cause of early-onset obesity. In an adult UK Caucasian population, the CRF-R1 C861T polymorphism is associated with increased BMI.

Age of Onset↗

Challenges in identifying genetic variation affecting susceptibility to type 2 diabetes: examples from studies of the calpain-10 gene.

Type 2 diabetes is a classic example of a complex disorder. It is strongly familial, but clearly arises as a consequence of the actions and interactions of many genetic and non-genetic factors. Type 2 diabetes is a common disorder, affecting 16 million Americans. It has a major impact on public health expenditures with more than 1 in 10 health care dollars spent on treating diabetes and its complications. Although a variety of therapies can be useful in treatment of type 2 diabetes, we remain sufficiently ignorant of the genetic risk factors to believe that identifying them will lead to better understanding of the primary physiology of the disorder, as well as to more specific and effective therapies. Moreover, identification of genetic risk factors may improve our ability to characterize more specific non-genetic risk factors for this disease that could be the targets for cost-effective prevention strategies. This manuscript reviews the challenges we face in moving from the linkage mapping of susceptibility genes for type 2 diabetes toward the identification of the genetic variation that actually affects risk to this disorder. I illustrate many of the challenges in designing, conducting and interpreting these studies by reviewing recent research conducted on the calpain-10 gene, implicated in positional cloning studies as a candidate gene for type 2 diabetes.

Adolescent↗

Polymorphisms in the apolipoprotein (apo) AI-CIII-AIV gene cluster: detection of genetic variation determining plasma apo AI, apo CIII and apo AIV concentrations.

We have examined the associations between levels of plasma apolipoprotein (apo) AI, apo CIII and apo AIV and genetic variation in the apo AI-CIII-AIV gene cluster in 162 boys and young men from Belgium aged from 7 to 23 years. Genotypes were determined for six restriction enzymes XmnI, PstI, SstI, PvuIIA-CIII, PvuIIB-AIV and XbaI, and for the G to A substitution at -75 bp in the 5' region of the apo AI gene. The polymorphism most strongly associated with apo AI levels was the G to A substitution (P = 0.025, R2 x 100 = 3.6%) confirming previous observations. The polymorphism most strongly associated with apo CIII levels was that of PvuIIA-CIII (P = 0.023, R2 x 100 = 2.9%) in the apo CIII gene. This novel association must be interpreted with caution until it has been confirmed in an independent sample. The polymorphism associated with the largest effect on apo AIV levels was that detected with XbaI in the apo AIV gene, but this association was not statistically significant. Previously reported associations between the SstI polymorphism and triglyceride levels, and between the PstI polymorphism and apo AI levels, were weakly detected in the present sample. Our results show that variation associated with some of the polymorphisms in the apo AI-CIII-AIV cluster makes a small, but statistically significant, contribution to the determination of apo AI and apo CIII levels in this sample of young men and boys. These observations may, in part, explain reported associations between polymorphisms in this gene cluster, differences in plasma lipid and lipoprotein levels, and prevalence of coronary artery disease.

Adolescent↗

Maintenance of genetic variation with a frequency-dependent selection model as compared to the overdominant model.

A frequency-dependent selection model proposed by Huang, Singh and Kojima (1971) was found to be more effective at maintaining genetic variation in a finite population than the overdominant model. The fourth moment parameter of the distribution of unfixed states showed that there was a more platykurtic distribution for the frequency-dependent model. This agreed well with the expected gene frequency change found for an infinite population.

Analysis of Variance↗

Genetic variation in clones of Pseudomonas pseudoalcaligenes after ten months of selection in different thermal environments in the laboratory.

The random amplification of polymorphic DNA (RAPD) method was used to examine genetic variation in experimental clones of Pseudomonas pseudoalcaligenes in two experimental groups, as well as their common ancestor. Six clones derived from a single colony of P. pseudoalcaligenes were cultured in two different thermal regimes for 10 months. Three clones in the Control group were cultured at constant temperature of 35 degrees C and another three clones in the High Temperature (HT) group were propagated at incremental temperature ranging from 41 to 47 degrees C for 10 months. A total of 45 RAPD primers generated 146 polymorphic markers. Analysis of molecular variance (AMOVA) revealed mild (11%) but significant (P < 0.001) genetic difference between the Control and the HT clones. Phylogenetic analysis based on pairwise genetic distances showed that the HT clones were more divergent from the ancestor and from each other than the Control clones, implying that the HT clones of P. pseudoalcaligenes may have evolved faster than the Control clones.

Genetic Variation↗

The comparative biology of genetic variation for conditional sex ratio behavior in a parasitic wasp, Nasonia vitripennis.

Using genetic markers, we tracked the sex ratio behavior of individual females of the parasitic wasp, Nasonia vitripennis, in foundress groups of size 1, 2, 4, 8 and 16. Comparison of 12 isofemale strains extracted from a natural population reveals significant between-strain heterogeneity of sex ratios produced in all sizes of foundress group. Under simple assumptions about population structure, this heterogeneity results in heterogeneity of fitnesses. The strains differ in their conditional sex ratio behavior (the sex ratio response of a female to foundress groups of different sizes). Females of some strains produce more males as foundress group size increases (up to size eight). Females of another strain produce more males when not alone but do not respond differentially to group size otherwise. Females of two other strains show no conditional sex ratio behavior. Females of only two strains behave differently in foundress groups of size 8 and 16. Correlation and regression analyses indicate that the strains differ significantly in their fit to the predictions of an evolutionarily stable strategy (ESS) model of conditional sex ratio behavior. Such heterogeneity contradicts the notion that females of this species possess conditonal sex ratio behavior that is optimal in the ESS sense. The results imply that this ESS model is useful but not sufficient for understanding the causal basis of the evolution of this behavior in this species. This is the first report on the sex ratio behavior of individual females in multiple foundress groups in any species of parasitic wasp. Data of this type (and not foundress group or "patch" sex ratios) are essential for testing evolutionary models that predict the sex ratio behaviors of individuals. We suggest that a test for an ESS model include the answers to two important questions: 1) is the model quantitatively accurate? and 2) is there reasonable evidence to indicate that natural selection has caused individuals to manifest the ESS behavior?

Animals↗