Forensic and genetic characterizations of diverse southern Thai populations based on 15 autosomal STRs

Southern Thailand is home to various populations; the Moklen, Moken and Urak Lawoi’ sea nomads and Maniq negrito are the minority, while the southern Thai groups (Buddhist and Muslim) are the majority. Although previous studies have generated forensic STR dataset for major groups, such data of the southern Thai minority have not been included; here we generated a regional forensic database of southern Thailand. We newly genotyped common 15 autosomal STRs in 184 unrelated southern Thais, including all minorities and majorities. When combined with previously published data of major southern Thais, this provides a total of 334 southern Thai samples. The forensic parameter results show appropriate values for personal identification and paternity testing; the probability of excluding paternity is 0.99999622, and the combined discrimination power is 0.999999999999999. Probably driven by genetic drift and/or isolation with small census size, we found genetic distinction of the Maniq and sea nomads from the major groups, which were closer to the Malay and central Thais than the other Thai groups. The allelic frequency results can strength the regional forensic database in southern Thailand and also provide useful information for anthropological perspective.

Exome sequencing of glioblastoma-derived cancer stem cells reveals rare clinically relevant frameshift deletion in MLLT1 gene

Background Glioblastoma multiforme (GBM) is a heterogeneous CNS neoplasm which causes significant morbidity and mortality. One reason for the poor prognostic outcome of GBM is attributed to the presence of cancer stem cells (CSC) which confer resistance against standard chemo- and radiotherapeutics modalities. Two types of GBM-associated CSC were isolated from the same patient: tumor core- (c-CSC) and peritumor tissue-derived cancer stem cells (p-CSC). Our experiments are focused on glioblastoma–IDH-wild type, and no disease-defining alterations were present in histone, BRAF or other genes. Methods In the present study, potential differences in genetic variants between c-CSC versus p-CSC derived from four GBM patients were investigated with the aims of (1) comparing the exome sequences between all the c-CSC or p-CSC to identify the common variants; (2) identifying the variants affecting the function of genes known to be involved in cancer origin and development. Results By comparative analyses, we identified common gene single nucleotide variants (SNV) in all GBM c-CSC and p-CSC, a potentially deleterious variant was a frameshift deletion at Gln461fs in the MLLT1 gene, that was encountered only in p-CSC samples with different allelic frequency. Conclusions We discovered a potentially harmful frameshift deletion at Gln461fs in the MLLT1 gene. Further investigation is required to confirm the presence of the identified mutations in patient tissue samples, as well as the significance of the frameshift mutation in the MLLT1 gene on GBM biology and response to therapy based on genomic functional experiments.

The Heart of Silk Road “Xinjiang,” Its Genetic Portray, and Forensic Parameters Inferred From Autosomal STRs

The Xinjiang Uyghur Autonomous Region of China (XUARC) harbors almost 50 ethnic groups including the Uyghur (UGR: 45.84%), Han (HAN: 40.48%), Kazakh (KZK: 6.50%), Hui (HUI: 4.51%), Kyrgyz (KGZ: 0.86%), Mongol (MGL: 0.81%), Manchu (MCH: 0.11%), and Uzbek (UZK: 0.066%), which make it one of the most colorful regions with abundant cultural and genetic diversities. In our previous study, we established allelic frequency databases for 14 autosomal short tandem repeats (STRs) for four minority populations from XUARC (MCH, KGZ, MGL, and UZK) using the AmpFlSTR® Identifiler PCR Amplification Kit. In this study, we genotyped 2,121 samples using the GoldenEye™ 20A Kit (Beijing PeopleSpot Inc., Beijing, China) amplifying 19 autosomal STR loci for four major ethnic groups (UGR, HAN, KZK, and HUI). These groups make up 97.33% of the total XUARC population. The total number of alleles for all the 19 STRs in these populations ranged from 232 (HAN) to 224 (KZK). We did not observe any departures from the Hardy–Weinberg equilibrium (HWE) in these populations after sequential Bonferroni correction. We did find minimal departure from linkage equilibrium (LE) for a small number of pairwise combinations of loci. The match probabilities for the different populations ranged from 1 in 1.66 × 1023 (HAN) to 6.05 × 1024 (HUI), the combined power of exclusion ranged from 0.999 999 988 (HUI) to 0.999 999 993 (UGR), and the combined power of discrimination ranged from 0.999 999 999 999 999 999 999 983 (HAN) to 0.999 999 999 999 999 999 999 997 (UGR). Genetic distances, principal component analysis (PCA), STRUCTURE analysis, and the phylogenetic tree showed that genetic affinity among studied populations is consistent with linguistic, ethnic, and geographical classifications.

Could the CCR5-Δ32 Mutation be Protective in SARS-CoV-2 Infection?

Increasing evidence points to host genetics as a factor in COVID-19 prevalence and outcome. CCR5 is a receptor for proinflammatory chemokines that are involved in host responses, especially to viruses. The CCR5-Δ32 minor allele is an interesting variant, given the role of CCR5 in some viral infections, particularly HIV-1. Recent studies of the impact of CCR5-Δ32 on COVID-19 risk and severity have yielded contradictory results. This ecologic study shows that the CCR5-Δ32 allelic frequency in a European population was significantly negatively correlated with the number of COVID-19 cases (p=0.035) and deaths (p=0.006) during the second pandemic wave. These results suggest that CCR5-Δ32 may be protective against SARS-CoV-2 infection, as it is against HIV infection, and could be predictive of COVID-19 risk and severity. Further studies based on samples from populations of different genetic backgrounds are needed to validate these statistically obtained findings.

Molecular surveillance of resistance to pyrethroids insecticides in Colombian Aedes aegypti populations

Introduction In Colombia, organochloride, organophosphate, carbamate, and pyrethroid insecticides are broadly used to control Aedes aegypti populations. However, Colombian mosquito populations have shown variability in their susceptibility profiles to these insecticides, with some expressing high resistance levels. Materials and methods In this study, we analyzed the susceptibility status of ten Colombian field populations of Ae. aegypti to two pyrethroids; permethrin (type-I pyrethroid) and lambda-cyhalothrin (type-II pyrethroid). In addition, we evaluated if mosquitoes pressured with increasing lambda-cyhalothrin concentrations during some filial generations exhibited altered allelic frequency of these kdr mutations and the activity levels of some metabolic enzymes. Results Mosquitoes from all field populations showed resistance to lambda-cyhalothrin and permethrin. We found that resistance profiles could only be partially explained by kdr mutations and altered enzymatic activities such as esterases and mixed-function oxidases, indicating that other yet unknown mechanisms could be involved. The molecular and biochemical analyses of the most pyrethroid-resistant mosquito population (Acacías) indicated that kdr mutations and altered metabolic enzyme activity are involved in the resistance phenotype expression. Conclusions In this context, we propose genetic surveillance of the mosquito populations to monitor the emergence of resistance as an excellent initiative to improve mosquito-borne disease control measures.

Genetic Relationships and Genome Selection Signatures Between Soybean Cultivars from Brazil and United States After Decades of Breeding

Soybeans are one of the most important crops worldwide. Brazil and the United States (US) are the world’s two biggest producers of this legume. The increase of publicly available DNA sequencing data as well as high-density genotyping data of multiple soybean germplasms has made it possible to understand the genetic relationships and identify genomics regions that underwent selection pressure during soy domestication and breeding. In this study, we analyzed the genetic relationships between Brazilian (N=235) and US soybean cultivars (N=675) released in different decades, and screened for genomic signatures between Brazilian and US cultivars. The population structure analysis demonstrated that the Brazilian germplasm has a narrower genetic base than the US germplasm. The US cultivars was grouped according to the maturity groups, while Brazilian cultivars were separated according to decades of releases. We found 73 SNPs that differentiate Brazilian and US soybean germplasm. Maturity-associated SNPs showed high allelic frequency differences between Brazil and US accessions. Other important loci were identified separating cultivars released before and after 1996 in Brazil. Our data showed important genomic regions under selection during decades of soybean breeding in Brazil and the US that should be targeted to adapt lines from different origins in these countries.

Prevalence of ABCB1 3435C>T polymorphism in the Cuban population

Objectives ABCB1 gene polymorphisms can modify P-glycoprotein function with clinical consequences. Methods The 3435C>T polymorphism prevalence was analyzed using oligonucleotide probes and next-generation sequencing in 421 unrelated healthy individuals living in Cuba. Data were stratified by gender, ethnic background and residence. The genotype and allelic frequencies were determined. Results The genotype distribution met the Hardy–Weinberg equilibrium assumption. The allelic frequency was 63.5% for the 3435C variant. The genotype frequencies were 41.1% for CC, 44.9% for CT and 14.0% for TT. The allele and genotype distributions differed between individuals living in La Habana and Santiago de Cuba (p<0.05) when ethnic background was analyzed. The allelic distribution was similar among Admixed and Black subjects, and they differed from Caucasians. The CC genotype was equally distributed among Admixed and Black subjects, and they differed from Caucasians. The TT genotype frequency differed between Caucasians and Admixed. The CT genotype was distributed differently among the three groups. Similar distribution was obtained in Brazilians, whereas some similarities were observed in African, Spanish and Chinese populations, consistent with the mixed Cuban ethnic origin. Conclusions This is the first report on allele and genotype frequencies of the 3435C>T polymorphism in Cuba, which may support personalized medicine programs.

Effect of CYP3A4, CYP3A5, MDR1 and POR Genetic Polymorphisms in Immunosuppressive Treatment in Chilean Kidney Transplanted Patients

Cyclosporine (CsA) and tacrolimus (TAC) are immunosuppressant drugs characterized by a narrow therapeutic range and high pharmacokinetic variability. The effect of polymorphisms in genes related to the metabolism and transport of these drugs, namely CYP3A4, CYP3A5, MDR1 and POR genes, has been evaluated in diverse populations. However, the impact of these polymorphisms on drug disposition is not well established in Latin American populations. Using TaqMan® probes, we determined the allelic frequency of seven variants in CYP3A4, CYP3A5, MDR1 and POR in 139 Chilean renal transplant recipients, of which 89 were treated with CsA and 50 with TAC. We tested associations between variants and trough and/or 2-hour concentrations, normalized by dose (C0/D and C2/D) at specific time points post-transplant. We found that CYP3A5*3/*3 carriers required lower doses of TAC. In TAC treated patients, most CYP3A5*3/*3 carriers presented higher C0/D and a high proportion of patients with C0 levels outside the therapeutic range relative to other genotypes. These results reinforce the value of considering CYP3A5 genotypes alongside therapeutic drug monitoring for TAC treated Chilean kidney recipients.

Polymorphic Investigation of ADCY2 and C7 Genes in Local Population of Oral Cancer

Single nucleotide polymorphisms (SNP) are responsible for genetic mutations. We studied genetic molecular variations and found an association of oral cancer with SNP of Adenylate Cyclase 2 (ADCY2) rs252546 and complement C7 (C7) rs1450656 genes in people of Southern Punjab, Pakistan. The study involves 100 cases of oral cancer and 100 healthy individuals. ADCY2 is found as a membrane-associated enzyme and C7 is involved in innate immunity. The process of genotyping was carried out by Tetra ARMS Primer PCR. The genetic variant of ADCY2 rs252546 has allelic origin G/A and C7 rs1450656 with C/T. The statistical analysis showed that the 51-60 years age group is significantly associated with oral cancer. The allelic frequency of ADCY2 rs252546 and C7 rs1450656 was calculated through Hardy Weinberg equilibrium. The homozygous mutant allele G of ADCY2 was more prevalent in cases and C allelic genotype was equally found in cases and controls. Other demographic and polymorphic studies indicated a significant association of variants of ADCY2 and C7 with oral cancer in the local population of Punjab. Variations in ADCY2 and C7 can be used as potential biomarkers and biological targets for oral cancer management strategies.

Comparison of Genetic Parameters among Selfed Lines and Random Mated Population A (PDM 53 x PDM 4441) and Population B (HKI 1105 x HKI 323) and Identification of Transgressive Segregants

The present study was conducted to compare the genetic variability parameters among selfed lines of population A (PDM 53 x PDM 4441) and population B (HKI 1105 x HKI 323) and also random mated population A (PDM 53 x PDM 4441) and random mated population B (HKI 1105 x HKI 323) using original inbred parents and three commercial checks, HM-4 (National check), CPB 468 and TENDER (Private check). High heritability coupled with high genetic advance was observed for number of cobs per plant, husked cob weight, dehusked cob weight, baby corn yield with and without husk per plant among selfed populations and a similar trend was observed in random mated populations except for ear length and days to 50 % silking. In total the variability observed was more in random mated populations than selfed lines because allelic frequency differences occur in random mated populations and the pool of gametes originating from male and female is different when compared to the pollen source in selfed populations. The frequency of transgressive segregants were more in random mated Population A (PDM 53 x PDM 4441) and the most promising transgressive segregant identified can be used in the further breeding programmes.