Genetic Landscape of VIP Pharmacogenomic Variants in the Kinh Vietnamese Population

Large scale human genome projects have created tremendous human genome databases for some well-studied populations. Vietnam has about 95 million people (the 14th largest country by population in the world) of which more than 86% are Kinh people. To date, genetic studies for Vietnamese people mostly rely on genetic information from other populations. Building a Vietnamese human genetic variation database is a must for properly interpreting Vietnamese genetic variants. To this end, we sequenced 105 whole genomes and 200 whole exomes of 305 unrelated Kinh Vietnamese (KHV) people. We also included 101 other previously published KHV genomes to build a Vietnamese human genetic variation database of 406 KHV people. The KHV database contains 24.81 million variants (22.47 million single nucleotide polymorphisms (SNPs) and 2.34 million indels) of which 0.71 million variants are novel. It includes more than 99.3% of variants with a frequency of >1% in the KHV population. Noticeably, the KHV database revealed 107 variants reported in the human genome mutation database as pathological mutations with a frequency above 1% in the KHV population. The KHV database (available at https://genomes.vn) would be beneficial for genetic studies and medical applications not only for the Vietnamese population but also for other closely related populations.

BackgroundLate‐onset Alzheimer Disease (LOAD) risk and prevalence differ by ancestral group. Furthermore, the frequency of APOE‐4 and its effect size on LOAD risk also differ by ancestry group. If these patterns are a function of evolutionary history, we may find ancestry group‐specific evidence of recent selection at the APOE locus or APOE eQTLs. This could provide us with additional insights into APOE function, specifically its pleiotropic effects and ethnic specific mechanisms of disease.MethodsWe used chromosome 19 sequence data from 2,504 unrelated individuals in 26 populations from the latest release of the 1000 Genomes Data (phased 30x coverage build 38 data), and we ran separate selection analyses in each population. We calculated two selection measures based on Extension of Haplotype Homozygosity (EHH): iHS (integrated haplotype score) and nSL (number of segregating sites by length). Scores were then normalized in bins of similar allele frequency (AF) to account for frequency effects on EHH. Loci in the top 1% of |iHS| and |nSL| scores were considered evidence of selection.ResultsAmong the two SNPs defining the APOE isoforms and 27 SNPs defining APOE EQTLs (29 sites in total) we observed 9 APOE eQTLs in the top 1% of iHS and three in the top 1% of nSL. Two SNPS demonstrated evidence of selection in both scores: rs1628394 in Kinh Vietnamese (in a SIPA1L3 intron) and rs2909088 in Han Chinese (in a ZFP30 intron). Neither of the APOE SNPs showed evidence of selection in any population.ConclusionsWe identified evidence of recent natural selection in APOE eQTLs in two East Asian populations: rs1628394 in Kinh Vietnamese and rs2909088 in Han Chinese. Prior work has established that rs1628394 is nominally associated with LOAD (p = 2.45 × 10‐3) and the genome Aggregation Database indicates that it is common in Africans (AF = 0.63), less common in Europeans (AF = 0.33), and least common in East Asians (AF = 0.13). The second SNP, rs2909088, is not associated with LOAD, but it is also less common in East Asians (AFEuropean = 0.87, AFAfrican = 0.69, and AFEastAsian = 0.38). Recent selection at rs1628394 may be enhancing the impact of APOE4 on LOAD development in Kinh Vietnamese.

Interpopulation differences in drug responses are well documented, and in some cases they correspond to differences in the frequency of associated genetic markers. Understanding the diversity of genetic markers associated with drug response across different global populations is essential to infer population rates of drug response or risk for adverse drug reactions, and to guide implementation of pharmacogenomic testing. Sri Lanka is a culturally and linguistically diverse nation, but little is known about the population genetics of the major Sri Lankan ethnic groups. The objective of this study was to investigate the diversity of pharmacogenomic variants in the major Sri Lankan ethnic groups. We examined the allelic diversity of more than 7000 variants in genes involved in drug biotransformation and response in the three major ethnic populations of Sri Lanka (Sinhalese, Sri Lankan Tamils, and Moors), and compared them with other South Asian, South East Asian, and European populations using Wright's Fixation Index, principal component analysis, and STRUCTURE analysis. We observed overall high levels of similarity within the Sri Lankan populations (median FST=0.0034), and between Sri Lankan and other South Asian populations (median FST=0.0064). Notably, we observed substantial differentiation between Sri Lankan and European populations for important pharmacogenomic variants related to warfarin (VKORC1 rs9923231) and clopidogrel (CYP2C19 rs4986893) response. These data expand our understanding of the population structure of Sri Lanka, provide a resource for pharmacogenomic research, and have implications for the clinical use of genetic testing of pharmacogenomic variants in these populations.

Clinical Outcomes for Patients with Severe Chronic Neutropenia Due to Mutations in the Gene for Neutrophil Elastase, ELANE

Kinh is the largest population in Vietnam. It belongs to Mon-Khmer linguistically, but there is no last word for its origin. There are three hypotheses for the homeland of Kinh. The formation of Kinh population is also hypothesized to have occurred by one of two different modes. One is demic diffusion of Mon-Khmer, the other is Daic population assimilated by Mon-Khmer. Population studies such as dermatoglyphics can be used to determine the relevant mode. Fingerprints, palm prints, and sole prints of 135 individuals from Kinh populations all over Vietnam were collected in this project. Principle component analysis and dendrogram analysis were done based on the dermatoglyphic data of populations from south China and Vietnam. Kinh Vietnamese was found to be quite close to Deang and Blang, which belong to the Mon-Khmer group, but are not closely related to the Daic populations. This study supports the demic diffusion mode of the formation of the Kinh population. The interaction with the Daic population was never a significant course in the formation of Kinh.

BackgroundAllopurinol (ALLO) exposes to mild (M) and severe (S) cutaneous adverse reactions (CARs). SCARS have been associated with HLA*B58 01 with various strength of across ethnicities. Little is known about...

BackgroundDeidentified newborn screening bloodspot samples (NBS) represent a valuable potential resource for genomic research if impediments to whole exome sequencing of NBS deoxyribonucleic acid (DNA), including the small amount of genomic DNA in NBS material, can be overcome. For instance, genomic analysis of NBS could be used to define allele frequencies of disease-associated variants in local populations, or to conduct prospective or retrospective studies relating genomic variation to disease emergence in pediatric populations over time. In this study, we compared the recovery of variant calls from exome sequences of amplified NBS genomic DNA to variant calls from exome sequencing of non-amplified NBS DNA from the same individuals.ResultsUsing a standard alignment-based Genome Analysis Toolkit (GATK), we find 62,000–76,000 additional variants in amplified samples. After application of a unique kmer enumeration and variant detection method (RUFUS), only 38,000–47,000 additional variants are observed in amplified gDNA. This result suggests that roughly half of the amplification-introduced variants identified using GATK may be the result of mapping errors and read misalignment.ConclusionsOur results show that it is possible to obtain informative, high-quality data from exome analysis of whole genome amplified NBS with the important caveat that different data generation and analysis methods can affect variant detection accuracy, and the concordance of variant calls in whole-genome amplified and non-amplified exomes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1747-2) contains supplementary material, which is available to authorized users.

Minor Subclones Harboring Small Insertions and Deletions Probably Due To Aberrant Splicing Can Frequently Be Detected By Deep Sequencing of The BCR-ABL Kinase Domain

Genomic DNA from 60 cases of acute myeloid leukaemia (AML) was screened for mutations in the c-kit gene. DNA from all 21 exons was subjected to polymerase chain reaction (PCR) amplification and analysis by conformation sensitive gel electrophoresis (CSGE); exons showing altered CSGE patterns were then sequenced. Mutations were identified only in those patients with inv(16) (3/7 cases) or t(8;21) (1/2 cases) and comprised three in-frame deletion plus insertion mutations (exon 8) and one point mutation (exon 10, GTA --> ATA, Val530Ile). Exons 8 and 10 were then analysed in 31 further cases of inv(16) (n = 14) and t(8;21) (n = 17), revealing four additional exon 8 in-frame deletion plus insertion mutations, all of which were in cases of inv(16). All exon 8 in-frame deletion plus insertion mutations (n = 7) involved the loss or replacement of the codon for Asp419 which is highly conserved cross species and is located in the receptor's extracellular domain. The high frequency of the c-kit proto-oncogene exon 8 deletion plus insertion mutations in AML suggests an essential role for this region of the receptor's extracellular domain. The association with inv(16) invites speculation as to the link between these two changes in the pathogenesis of AML.

Genetic defects in the nef gene are associated with Korean Red Ginseng intake: monitoring of nef sequence polymorphisms over 20 years

The effect of SERPINF1 in-frame mutations in osteogenesis imperfecta type VI

Medication safety and efficacy-related pharmacogenomic research play a critical role in precision medicine. This study comprehensively analyzed the pharmacogenomic profiles of the central Han Chinese population in the context of medication safety and efficacy and compared them with other global populations. The ultimate goal is to improve medical treatment guidelines. We performed whole-genome sequencing in 487 Han Chinese individuals and investigated the allele frequencies of pharmacogenetic variants in 1,731 drug response-related genes. We identified 2,139 (81.18%) previously reported variants in our population with annotations in the PharmGKB database. The allele frequencies of these 2,139 clinical-related variants were similar to those in other East Asian populations but different from those in other global populations. We predicted the functional effects of nonsynonymous variants in the 1,731 pharmacogenes and identified 1,281 novel and 4,442 previously reported deleterious variants. Of the 1,281 novel deleterious variants, five are common variants with an allele frequency >5%, and the rest are rare variants with an allele frequency <5%. Of the 4,442 known deleterious variants, the allele frequencies were found to differ from those in other populations, of which 146 are common variants. In addition, we found many variants in non-coding regions, the functions of which require further investigation. This study compiled a large amount of data on pharmacogenomic variants in the central Han Chinese population. At the same time, it provides insight into the role of pharmacogenomic variants in clinical medication safety and efficacy.

KEYWORDS ARMS-PCR. Case/Control. G6PD Deficiency. Viangchan. Vietnamese ABSTRACT As the most common missense mutation cause of G6PD deficiency in Vietnamese, Viangchan (Val291Met) mutation can be used as the marker for development of the molecular diagnostic to diagnose this disease. To confirm Viangchan as the marker for diagnosis a case/control study is carried out. This study confirmed the role of Viangchan mutation in G6PD deficiency in Vietnamese and indicate the necessary of development of new molecular method for diagnosis of the diseases replace the fluorescence test recently as their limitation in identify G6PD patients. An AMRS-PCR was designed to screen Viangchan mutation in a 318 cases and 210 controls sample set. The result showed that Viangchan mutation occupied 26.7% in the population in this study, while in the G6PD deficient population it occupied 24%. The association analysis showed that the risk allele A in this mutation is strongly associated with G6PD deficiency in Vietnamese Kinh population (OR = 42.8; 95% CI (13.5-135.5); p<0.0001). The genotypes which contained risk alleles were also strongly associated with the disease (OR=22.4; 95% CI (6.96-71.99); p<0.0001). This study confirmed that the Viangchan is the most common causative mutation for G6PD deficiency in Vietnamese Kinh. Thus this mutation can be used as the indicator for diagnosis of G6PD in Vietnamese Kinh.

KEYWORDS ARMS-PCR. Case/Control. G6PD Deficiency. Viangchan. Vietnamese ABSTRACT As the most common missense mutation cause of G6PD deficiency in Vietnamese, Viangchan (Val291Met) mutation can be used as the marker for development of the molecular diagnostic to diagnose this disease. To confirm Viangchan as the marker for diagnosis a case/control study is carried out. This study confirmed the role of Viangchan mutation in G6PD deficiency in Vietnamese and indicate the necessary of development of new molecular method for diagnosis of the diseases replace the fluorescence test recently as their limitation in identify G6PD patients. An AMRS-PCR was designed to screen Viangchan mutation in a 318 cases and 210 controls sample set. The result showed that Viangchan mutation occupied 26.7% in the population in this study, while in the G6PD deficient population it occupied 24%. The association analysis showed that the risk allele A in this mutation is strongly associated with G6PD deficiency in Vietnamese Kinh population (OR = 42.8; 95% CI (13.5-135.5); p<0.0001). The genotypes which contained risk alleles were also strongly associated with the disease (OR=22.4; 95% CI (6.96-71.99); p<0.0001). This study confirmed that the Viangchan is the most common causative mutation for G6PD deficiency in Vietnamese Kinh. Thus this mutation can be used as the indicator for diagnosis of G6PD in Vietnamese Kinh.

A breeding programme of aromatic vanilla, dating back to 1944, was conducted in Ambohitsara, Antalaha, SAVA (Sambava, Antalaha, Vohemara, Andapa) – Madagascar. Imported, local, wild and cultivated vanillas were used as progenitors and thousands of hybrids were generated. However, this germplasm has not undergone any genetic evaluation, and it appears that these valuable genetic resources have been dispersed or lost after the end of the programme (2000). This study aims to investigate the genetic diversity and structure of rescued genotypes currently held in a local collection in Antalaha. Double digest restriction associated-site (RAD)-seq (ddRAD)-seq protocol was applied, providing 865 million read sequences from 56 accessions. The ddRAD sequences have been deposited to the SRA archive of NCBI. From the data, 23,701 filtered concordant common Single Nucleotide Polymorphisms (SNPs) were identified using the three widely used tools (Stacks, BCFtools, Genome Analysis ToolKit - GATK) for short-read library sequencing. These SNPs were used for germplasm evaluation. Clustering analysis segregated samples into five genetic groups: Vanilla planifolia, Vanilla pompona, hybrid Tsitaitra, Vanille Banane and the phenotype Tsivaky. Our analysis revealed distinct subgroups within V. pompona and Tsitaitra, emphasizing the importance of further characterization to accurately reflect the genetic diversity and facilitate better utilization of these accessions in future research and germplasm management. The presence of private alleles in all groups (from 487 to 2866) indicated that populations were diverging and represented a large gene pool that could be useful for future breeding efforts. The genetic data obtained from this study offers valuable insights into the genetic diversity and structure of the vanilla population, with potential applications in breeding and conservation efforts.