Genetic Distribution of Five Spinocerebellar Ataxia Microsatellite Loci in Mexican Native American Populations and Its Impact on Contemporary Mestizo Populations

Spinocerebellar ataxias (SCAs) conform a heterogeneous group of neurodegenerative disorders with autosomal dominant inheritance. Five of the most frequent SCAs are caused by a CAG repeat expansion in the exons of specific genes. The SCAs incidence and the distribution of polymorphic CAG alleles vary among populations and ethnicities. Thus, characterization of the genetic architecture of ethnically diverse populations, which have undergone recent admixture and demographic events, could facilitate the identification of genetic risk factors. Owing to the great ethnic diversity of the Mexican population, this study aimed to analyze the allele frequencies of five SCA microsatellite loci (SCA1, SCA2, SCA3, SCA6, and SCA7) in eleven Mexican Native American (MNA) populations. Data from the literature were used to compare the allelic distribution of SCA loci with worldwide populations. The SCA loci allelic frequencies evidenced a certain genetic homogeneity in the MNA populations, except for Mayans, who exhibited distinctive genetic profiles. Neither pathological nor large normal alleles were found in MNA populations, except for the SCA2 pre-mutated allele in the Zapotec population. Collectively, our findings demonstrated the contribution of the MNA ancestry in shaping the genetic structure of contemporary Mexican Mestizo populations. Our results also suggest that Native American ancestry has no impact on the origin of SCAs in the Mexican population. Instead, the acquisition of pathological SCA alleles could be associated with European migration.

Association of the caprine calpastatin MspI polymorphism with growth and reproduction traits in Saanen goats

This study was designed to evaluate the effects of calpastatin (CAST) MspI polymorphism on some growth and reproduction traits, including birth weight, first breeding weight, litter size, and average daily weight gain in Saanen goats. In this sense, blood samples obtained from 73 purebred female Saanen goats were used for genotyping. Genomic DNA was isolated by the phenol-chloroform method and used to determine CAST genotypes, including MM, MN, and NN, by means of the PCR-RFLP method. The population genetic parameters were estimated based on allelic distribution and the data were statistically analysed using analysis of variance (ANOVA) using a general linear model (GLM). Results revealed that N allele frequency was remarkably high (0.64) and the MM genotype was not present. The frequency of the heterozygous genotype was 59.62%. Concerning ANOVA results, significant differences were found between genotypes of the CAST locus concerning birth weight (P<0.05). In this respect, animals with the NN genotype were associated with higher birth weight means (2.85±0.29 kg) compared to heterozygous animals (2.53±0.24 kg). There was no significant association between the CAST marker and any of the remaining phenotypic traits evaluated. The present results suggest that focusing on this genomic region may be particularly useful in improving birth weight in goats which can be considered as an early indicator of post-weaning animal growth and survival.

Differential patterns of diversity at neutral and adaptive loci in endangered Rhodeus pseudosericeus populations

Given the fact that threatened species are often composed of isolated small populations, spatial continuity or demography of the populations may be major factors that have shaped the species’ genetic diversity. Thus, neutral loci have been the most commonly-used markers in conservation genetics. However, the populations under the influence of different environmental factors may have evolved in response to different selective pressures, which cannot be fully reflected in neutral genetic variation. Rhodeus pseudosericeus, a bitterling species (Acheilognathidae; Cypriniformes) endemic to the Korean Peninsula, are only found in some limited areas of three rivers, Daecheon, Han and Muhan, that flow into the west coast. Here, we genotyped 24 microsatellite loci and two loci (DAB1 and DAB3) of MHC class II peptide-binding β1 domain for 222 individuals collected from seven populations. Our microsatellite analysis revealed distinctive differentiation between the populations of Daecheon and Muhan Rivers and the Han River populations, and populations were structured into two subgroups within the Han River. Apparent positive selection signatures were found in the peptide-binding residues (PBRs) of the MHC loci. The allelic distribution of MHC showed a degree of differentiation between the populations of Daecheon and Muhan Rivers and the Han River populations, partially similar to the results obtained for microsatellites, however showed rather complex patterns among populations in the Han River. Considering the apparent differences in the distribution of supertypes obtained based on the physicochemical differences induced by the polymorphisms of these PBRs, the differentiation in DAB1 between the two regional groups may result in the differences in immune function. No differentiation between these two regions was observed in the supertyping of DAB3, probably indicating that only DAB1 was associated with the response to locally specialized antigenic peptides.

C9orf72-G4C2 Intermediate Repeats and Parkinson’s Disease; A Data-Driven Hypothesis

Pathogenic C9orf72-G4C2 repeat expansions are associated with ALS/FTD, but not with Parkinson’s disease (PD); yet the possible link between intermediate repeat lengths and PD remains inconclusive. We aim to study the potential involvement of these repeats in PD. The number of C9orf72-repeats were determined by flanking and repeat-primed PCR assays, and the risk-haplotype was determined by SNP-array. Their association with PD was assessed in a stratified manner: in PD-patients-carriers of mutations in LRRK2, GBA, or SMPD1 genes (n = 388), and in PD-non-carriers (NC, n = 718). Allelic distribution was significantly different only in PD-NC compared to 600 controls when looking both at the allele with higher repeat’s size (p = 0.034) and at the combined number of repeats from both alleles (p = 0.023). Intermediate repeats (20–60 repeats) were associated with PD in PD-NC patients (p = 0.041; OR = 3.684 (CI 1.05–13.0)) but not in PD-carriers (p = 0.684). The C9orf72 risk-haplotype, determined in a subgroup of 588 PDs and 126 controls, was observed in higher frequency in PD-NC (dominant model, OR = 1.71, CI 1.04–2.81, p = 0.0356). All 19 alleles within the risk-haplotype were associated with higher C9orf72 RNA levels according to the GTEx database. Based on our data, we suggest a model in which intermediate repeats are a risk factor for PD in non-carriers, driven not only by the number of repeats but also by the variants’ genotypes within the risk-haplotype. Further studies are needed to elucidate this possible role of C9orf72 in PD pathogenesis.

The efficacy of diuretics in complex treatment of patients with hypertension according to the Gly460Trp polymorphism of the α-adducin gene

The aim of the study was to investigate the effect of thiazide diuretics on blood pressure (BP) depending on Gly460Trp ADD1 gene polymorphism in arterial hypertension (AH) patients of the Ukrainian population in order to predict their individual treatment efficacy. Material and methods. The study included 232 persons: 120 patients with verified stage II AH and 112 healthy individuals. Restriction fragment length polymerase chain reaction (PCR-RFLP) was used to detect genotype (the Gly460Trp-polymorphic locus of the ADD1 gene). The patients received standard therapy, which included ACE inhibitor – ramipril 5 mg, calcium channel antagonist – amlodipine 5 mg, statin – atorvastatin 20 mg, acetylsalicylic acid 75 mg. The patients were randomized into two groups: group I (60 persons) additionally taking treatment with 1.5 mg of indapamide retard and group II (60 persons) – with 25 mg of hydrochlorothiazide. The dynamic reduction of blood pressure has been assessed every 4 weeks for 2 months. Results. Among 120 patients with AH, 91 persons (75.8 %) were homozygous for the G allele (GG), 26 persons (21.7 %) – heterozygous (GT) and 3 persons (2.5 %) – homozygous for the T allele (TT), while the G allele frequency in patients with hypertension was 0.87, and the T allele – 0.13. 98 healthy individuals (87.5 %) were homozygous for the G allele, 13 individuals (11.6 %) were heterozygous, and 1 person (0.9 %) was homozygous for the T allele. The carrier frequency of the G and T alleles was 0.93 and 0.07, respectively. Allelic distribution indicated the predominance of the G allele carriers by Gly460Trp polymorphism of the ADD1 gene among the Ukrainian population, regardless of whether AH symptoms were present. It is noteworthy that the number of the T allele carriers was 2 times large among symptomatic patients than that among healthy individuals. In patients with the T allele, the hypotensive efficacy of indapamide was almost 3 times higher than that in patients with the G allele. The antihypertensive effect of hydrochlorothiazide in patients with the GT and TT genotypes was 2 times greater than that in the GG genotype carriers depending on the presence of the T allele G460T polymorphism of ADD1 gene in the genotype. Conclusions. Allelic distribution indicates the predominance of the G allele carriers by Gly460Trp ADD1 gene polymorphism among the Ukrainian population, regardless of whether AH symptoms are present. Among patients with AH, the accumulation of the T allele G460T polymorphic marker of the α-adducin gene is 2 times more than that in healthy individuals. Patients carrying the T allele demonstrate 2 times higher hypotensive efficacy of indapamide compared with hydrochlorothiazide.

Polymorphisms of Interleukin-6 and Interleukin-8 Are Not Associated with Parkinson’s Disease in Taiwan

Background: Studies have suggested that cytokines are crucial mediators in the pathogenesis of Parkinson’s disease (PD). The multifunctional cytokine interleukin (IL)-6 and its single nucleotide polymorphisms (SNPs) were found to have an impact on the development of PD. However, different studies in associations of IL-6 genetic variants with PD showed inconsistent results and it has never been explored in a Taiwanese population. Both IL-1α and IL-8 contribute to the same inflammation pathway. IL-1α genetic polymorphism has an effect on late-onset PD in Taiwan, whereas the associations of IL-8 genetic variants with PD in Taiwan remain to be investigated. Methods: This study examined the frequencies of polymorphisms within the critical promoter areas of the proinflammatory cytokine genes: IL-6 G-174C (rs1800795) and IL-8 A-251T (rs4073) in Taiwanese PD patients compared with age-and gender-matched healthy subjects. Comparisons were also made in genotype and allele frequencies of IL-6 G-174C (rs1800795) and IL-8 A-251T (rs4073) among different populations in previous studies. Results: In total, 1120 subjects, including 509 PD patients (female/male: 259/250) and 511 control subjects (female/male: 252/259), were recruited. We found no statistically significant differences in IL-6 G-174C (rs1800795) or IL-8 A-251T (rs4073) genotypic and allelic distribution between PD and controls, even after being stratified by age at onset and gender. Conclusions: The results did not demonstrate any association of IL-6 G-174C (rs1800795) or IL-8 A-251T (rs4073) with PD in a Taiwanese population. Despite the negative results, this is the first study in associations of IL-6 G-174C (rs1800795) and IL-8 A-251T (rs4073) with PD in Taiwan. The relevance of genetic variants of IL-6 G-174C (rs1800795) or IL-8 A-251T (rs4073) on PD susceptibility warrants further investigation.

Association between the FTO A/T Polymorphism and Elite Athlete Status in Caucasian Swimmers

The FTO A/T polymorphism (rs9939609) has been strongly associated with body mass-related traits in nonathletic populations, but rarely with elite athletic performance. The aim of the study was to investigate the association between the A/T polymorphism and athlete status in elite swimmers. Polish swimmers (n = 196) who competed in national and international competition at short- (SDS; 50–200 m; n = 147) and long-distance events (LDS; ≥400 m; n = 49) were recruited. The control group included 379 unrelated, sedentary young participants. The participants were all Caucasians. Genotyping was carried out using real-time PCR. It was found that the chance of being an elite swimmer was lower in carriers of the AT and AA genotype compared with TT homozygotes (1.5 and 2.0 times, respectively). These findings were confirmed in an allelic association; the A allele was less frequent in the swimmers compared with controls (p = 0.004). However, when SDS were compared against LDS, no significant differences were observed in genotypic and allelic distribution. The results of our experiment suggest that the variation within the FTO gene can affect elite athlete status. It was demonstrated that harboring the T allele may be beneficial for achieving success in a sport such as swimming.

Sex-Related Differences in Allelic Frequency of the Human Beta T Cell Receptor SNP rs1800907: A Retrospective Analysis from Milan Metropolitan Area

This paper aims at retrospectively re-analyzing the different distribution, between males and females, in the allelic frequency of the human β T cell receptor (TCR β) single nucleotide polymorphism (SNPs) rs1800907 in Caucasian patients in the Milan metropolitan area. The allelic frequency significantly differed between sexes. Females showed higher frequency of C/C genotype than males, but lower T/C genotype (p < 0.0001). Heterozygous (T/C) versus homozygous (T/T + C/C) genotypes resulted in a different distribution of frequencies in males than in females, the latter possessing higher homozygosis (p < 0.0001). Within the limitations of this work (small number of included studies that concerned just a specific geographical area), allelic distribution according to sex might account the role of TCRβ-related SNPs in autoimmune diseases and further investigations are required to explain better this genetic background, in the perspective of a sex-related T cell immune responsiveness and auto-immunity.

Assessing adaptive requirements and breeding potential of spelt under Mediterranean environment

The rising demand for spelt wheat (Triticum aestivum ssp. spelta) as a high-value grain crop has raised interest in its introduction into non-traditional spelt growing areas. This study aimed to assess adaptive constrains of spelt under short Mediterranean season. At first screening of a wide spelt collection for phenology and allelic distribution at the photoperiod (PPD) and vernalization (VRN) loci was done. In addition an in-depth phenotypic evaluation of a selected panel (n = 20) was performed, including agronomically important traits and concentration of grain mineral (GMC) and grain protein (GPC) content. Results from both wide screening and in-depth in panel (group of 18 spelt lines and two bread wheat lines) evaluation shows that the major adaptive constraint for spelt under Mediterranean conditions is late heading, caused by day length sensitivity, as evident from phenology and allelic profile (PPD and VRN). All lines carrying the photoperiod-sensitive allele (PPD-D1b) were late flowering (> 120DH). Based on the panel field evaluations those consequently suffer from low grain yield and poor agronomic performances. As for minerals, GMC for all but Zn, significantly correlated with GPC. In general, GMC negatively correlated with yield which complicated the assessment of GMC per-se and challenge the claim for higher mineral content in spelt grains. The exceptions were, Fe and Zn, which did not correlate with yield. Spelt lines showing high Fe and Zn concentration in a high-yield background illustrate their potential for spelt wheat breeding. Improving spelt adaptation to Mediterranean environments could be mediated by introducing the insensitive-PPD-D1a allele to spelt wheat background. Following this breeding path spelt could better compete with bread wheat under short season with limited and fluctuating rain fall.