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1.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(4): 351-360, 2021 Apr 28.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-33967080

RESUMEN

OBJECTIVES: Due to the genetic feature of high diversity than other DNA markers, short tandem repeat (STR) plays key roles in forensic, anthropology, and population genetics. Newly introduced multiple STR kit is more valuable because of the greatly improved discriminatory power with the increase in the number of STR loci. The genetic polymorphic data are essential for the application and research in specific population. This study aims to investigate the genetic polymorphism of Han population residing in Yuncheng district, Shanxi Province, to evaluate the application of 23 STR loci in forensic personal identification and paternity test, and to explore the genetic relationship of Han population between Yuncheng and other populations. METHODS: A total of 23 STR loci were amplified from 525 healthy unrelated individuals from the Han nationality in Yuncheng, Shanxi Province using the AGCU EX25 amplification kit. The products were detected and separated by ABI 3500 Genetic Analyzer. Alleles were genotyped by GeneMapper ID (Version 3.2) software, and corresponding frequencies and forensic parameters were calculated. We calculated the genetic distance and plotted the neighboring-joining tree with other 13 population. RESULTS: The allele frequency of the 23 STRs ranged from 0.0010 to 0.5090. No deviation from Hardy-Weinberg equilibrium (P>0.05) and linkage disequilibrium was observed. The cumulative discriminatory power (CPD), cumulative power of exclusion for trios (CPEtrio)and cumulative Power of exclusion for duos (CPEduo) with total 23 STRs were 1-1.305 263 374 8×10-27, 1-2.583 152 052 2×10-10 and 1-1.193 637 500 4×10-6, respectively. Comprehensive population comparison showed that Shanxi Yuncheng Han nationality was genetically closer to populations of the same linguistic family or geographically close proximity, such as Shaanxi Weinan Han, Liaoning Han, and Ningbo Han nationality while relatively far away from different linguistic ethnic groups and geographically distant populations like Xinjiang Uygur and Guangdong Han nationality. CONCLUSIONS: These 23 STRs are highly genetic polymorphic and informative in the Han population of Yuncheng, Shanxi Province, which can provide basic data for forensic personal identification, paternity testing, and population genetic research.


Asunto(s)
Grupo de Ascendencia Continental Asiática , Repeticiones de Microsatélite , Grupo de Ascendencia Continental Asiática/genética , China , Grupos Étnicos/genética , Frecuencia de los Genes , Sitios Genéticos , Genética de Población , Humanos , Repeticiones de Microsatélite/genética , Polimorfismo Genético
2.
J Int Med Res ; 49(4): 3000605211000892, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33827324

RESUMEN

OBJECTIVE: Mutations in GJB2, SLC26A4, and mitochondrial (mt)DNA 12S rRNA genes are the main cause of nonsyndromic hearing impairment. The present study analyzed these mutations in ethnic minority and Han Chinese patients with nonsyndromic hearing impairment from Qinghai, China. METHODS: The SNPscan assay was used to analyze mutation spectra and frequencies in the two patient groups. RESULTS: GJB2 mutations were detected in 9.5% (20/210) of minority patients and 20.88% (48/230) of Han Chinese patients. The most common Han Chinese GJB2 variants were c.235delC and c.299_300delAT, whereas c.235delC and c.109G > A were the most prevalent in minority patients. SLC26A4 mutations were detected in 5.71% (12/210) of minority patients and 14.35% (33/230) of Han Chinese patients, and mtDNA 12S rRNA mutations were detected in 4.28% (9/210) of minority patients and 9.13% (21/230) of Han Chinese patients. CONCLUSIONS: These data indicate that the mutation frequencies of three deafness-associated genes were significantly higher in Han Chinese patients than in minority patients. Moreover, the GJB2 mutation spectrum was shown to differ between these two patient groups.


Asunto(s)
Sordera , Grupos Étnicos , Grupo de Ascendencia Continental Asiática/genética , China , Conexinas/genética , Análisis Mutacional de ADN , Sordera/genética , Grupos Étnicos/genética , Humanos , Grupos Minoritarios , Mutación
3.
Med Sci Monit ; 27: e928503, 2021 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-33677465

RESUMEN

BACKGROUND The association between leptin receptor (LEPR) polymorphisms and keloids is still unclear. Our study aimed to explore the association between LEPR gene polymorphisms and keloids in the Chinese Han population. MATERIAL AND METHODS We implemented a case-control study in a cohort of 352 keloid patients and 299 healthy controls to analyze the correlation between 4 SNPs (rs1137101, rs1938496, rs6588147, and rs7555955) and keloids. Genomic DNA was extracted from peripheral blood by using TGuide M16 (Tiangen). Genotyping of LEPR SNPs was performed using an improved multiple ligase detection reaction (iMLDR) by Shanghai Genesky Bio-Tech Co., Ltd. RESULTS We found that patients caring the AA genotype of rs1137101 and the CC genotype rs1938496 tend to have the increased risk of keloids (P=0.026, P=0.047). Carrying the GA, AA gene type, and G allele frequencies of rs7555955, patients were more likely to have to keloids (P=0.030, P=0.016, P=0.018, respectively). There were no significant differences in genotype distribution and allele frequencies of rs6588147 between cases and controls. The association of rs1137101 and rs7555955 under dominant, recessive, and allele models exhibited significant differences among family-history keloid patients, no-family-history keloid groups, and normal controls (χ²=6.471, P=0.039; χ²=6.477, P=0.039; χ²=6.197, P=0.045, respectively). Similarly, the OR of rs1137101 in the recessive model was significantly higher in patients with a family history of keloids than those in controls. Nonetheless, there are significant ORs of rs1938496 and rs6588147 among the mild-moderate keloid, severe keloid, and control groups. CONCLUSIONS The LEPR gene polymorphisms are associated with keloid formation and severity, especially in patients with a positive family history.


Asunto(s)
Queloide/genética , Receptores de Leptina/genética , Adulto , Grupo de Ascendencia Continental Asiática/genética , Estudios de Casos y Controles , China , Estudios de Cohortes , Grupos Étnicos/genética , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Queloide/metabolismo , Masculino , Polimorfismo de Nucleótido Simple/genética , Receptores de Leptina/metabolismo
4.
Mol Genet Genomics ; 296(3): 631-651, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33650010

RESUMEN

Trans-Eurasian cultural and genetic exchanges have significantly influenced the demographic dynamics of Eurasian populations. The Hexi Corridor, located along the southeastern edge of the Eurasian steppe, served as an important passage of the ancient Silk Road in Northwest China and intensified the transcontinental exchange and interaction between populations on the Central Plain and in Western Eurasia. Historical and archeological records indicate that the Western Eurasian cultural elements were largely brought into North China via this geographical corridor, but there is debate on the extent to which the spread of barley/wheat agriculture into North China and subsequent Bronze Age cultural and technological mixture/shifts were achieved by the movement of people or dissemination of ideas. Here, we presented higher-resolution genome-wide autosomal and uniparental Y/mtDNA SNP or STR data for 599 northwestern Han Chinese individuals and conducted 2 different comprehensive genetic studies among Neolithic-to-present-day Eurasians. Genetic studies based on lower-resolution STR markers via PCA, STRUCTURE, and phylogenetic trees showed that northwestern Han Chinese individuals had increased genetic homogeneity relative to northern Mongolic/Turkic/Tungusic speakers and Tibeto-Burman groups. The genomic signature constructed based on modern/ancient DNA further illustrated that the primary ancestry of the northwestern Han was derived from northern millet farmer ancestors, which was consistent with the hypothesis of Han origin in North China and more recent northwestward population expansion. This was subsequently confirmed via excess shared derived alleles in f3/f4 statistical analyses and by more northern East Asian-related ancestry in the qpAdm/qpGraph models. Interestingly, we identified one western Eurasian admixture signature that was present in northwestern Han but absent from southern Han, with an admixture time dated to approximately 1000 CE (Tang and Song dynasties). Generally, we provided supporting evidence that historic Trans-Eurasian communication was primarily maintained through population movement, not simply cultural diffusion. The observed population dynamics in northwestern Han Chinese not only support the North China origin hypothesis but also reflect the multiple sources of the genetic diversity observed in this population.


Asunto(s)
Grupo de Ascendencia Continental Asiática/genética , Genoma/genética , China , Cromosomas Humanos Y/genética , ADN Antiguo , ADN Mitocondrial/genética , Grupos Étnicos/genética , Genética de Población/métodos , Estudio de Asociación del Genoma Completo/métodos , Migración Humana , Humanos , Filogenia , Polimorfismo de Nucleótido Simple/genética
5.
Nat Commun ; 12(1): 1639, 2021 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-33712626

RESUMEN

Conventional human leukocyte antigen (HLA) imputation methods drop their performance for infrequent alleles, which is one of the factors that reduce the reliability of trans-ethnic major histocompatibility complex (MHC) fine-mapping due to inter-ethnic heterogeneity in allele frequency spectra. We develop DEEP*HLA, a deep learning method for imputing HLA genotypes. Through validation using the Japanese and European HLA reference panels (n = 1,118 and 5,122), DEEP*HLA achieves the highest accuracies with significant superiority for low-frequency and rare alleles. DEEP*HLA is less dependent on distance-dependent linkage disequilibrium decay of the target alleles and might capture the complicated region-wide information. We apply DEEP*HLA to type 1 diabetes GWAS data from BioBank Japan (n = 62,387) and UK Biobank (n = 354,459), and successfully disentangle independently associated class I and II HLA variants with shared risk among diverse populations (the top signal at amino acid position 71 of HLA-DRß1; P = 7.5 × 10-120). Our study illustrates the value of deep learning in genotype imputation and trans-ethnic MHC fine-mapping.


Asunto(s)
Aprendizaje Profundo , Diabetes Mellitus Tipo 1/genética , Predisposición Genética a la Enfermedad/genética , Antígenos HLA/genética , Complejo Mayor de Histocompatibilidad/genética , Alelos , Grupos de Población Continentales , Grupos Étnicos/genética , Estudio de Asociación del Genoma Completo , Genotipo , Antígenos de Histocompatibilidad Clase I/genética , Antígenos de Histocompatibilidad Clase II/genética , Humanos , Desequilibrio de Ligamiento
6.
Med Sci Monit ; 27: e928455, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33583939

RESUMEN

BACKGROUND The IRF5 and TYK2 gene polymorphisms are associated with autoimmune diseases. However, the relationship between the IRF5 and TYK2 gene polymorphisms and RA risk in the Chinese Han population was inconsistent. MATERIAL AND METHODS A total of 578 RA patients (case group) and 578 healthy controls (control group) were assessed in a case-control study. Genotyping of IRF5 (Exon 6 insertion/deletion (in/de), rs2004640, rs2070197, rs10954213) and TYK2 (rs280500, rs280519, rs280521, rs8108236, rs12720253) was performed by direct sequencing method. Data analysis was performed by SHEsis. RESULTS The rs2004640T allele (P=0.0003) and the dominant (P=0.001) and recessive (P=0.01) models of rs2004640 were associated with RA risk after stringent Bonferroni correction (0.05/4). The IRF5 exon 6 (in), rs2070197 and rs10954213 were not associated with RA (P>0.05). Two haplotypes of IRF5 (DTAT and DTGG) were associated with RA susceptibility (P<0.05). In addition, the frequencies of TYK2 rs280500A, rs280521A, and rs8108236A were significantly higher in the RA group compared with the control group (P<0.05). TYK2 rs280500, rs280521, and rs8108236 were associated with RA susceptibility in the dominant model, but the same was not observed for rs280519 and rs12720253 (P<0.05). Furthermore, 3 risk haplotypes (AAAGT, AGGAT, and GAAAT) and a protective haplotype (GAGGT) of TYK2 gene were associated with RA susceptibility (P<0.05). CONCLUSIONS Our results suggest that IRF5 rs2004640, TYK2 rs280500, rs280521, rs8108236, and haplotypes IRF5 (DTAT and DTGG) and TYK2 (AAAGT, AGGAT, GAAAT, and GAGGT) are susceptible factors for RA in a Chinese Han population.


Asunto(s)
Artritis Reumatoide/genética , Factores Reguladores del Interferón/genética , TYK2 Quinasa/genética , Adulto , Alelos , Artritis Reumatoide/metabolismo , Grupo de Ascendencia Continental Asiática/genética , Estudios de Casos y Controles , China/epidemiología , Grupos Étnicos/genética , Femenino , Predisposición Genética a la Enfermedad/genética , Genotipo , Haplotipos/genética , Humanos , Factores Reguladores del Interferón/metabolismo , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , TYK2 Quinasa/metabolismo
7.
Mol Genet Genomics ; 296(3): 581-590, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33580820

RESUMEN

Aiming to determine their ancestry diagnostic potential, we selected two sets of nuclear deletion/insertion polymorphisms (DIPs), including 30 located on autosomal chromosomes and 33 on the X chromosome. We analysed over 200 unrelated Argentinean individuals living in urban areas of Argentina. As in most American countries, the extant Argentinean population is the result of tricontinental genetic admixture. The peopling process within the continent was characterised by mating bias involving Native American and enslaved African females and European males. Differential results were detected between autosomal DIPs and X-DIPs. The former showed that the European component was the largest (77.8%), followed by the Native American (17.9%) and African (4.2%) components, in good agreement with the previously published results. In contrast, X-DIPs showed that the European genetic contribution was also predominant but much smaller (52.9%) and considerably larger Native American and African contributions (39.6% and 7.5%, respectively). Genetic analysis revealed continental genetic contributions whose associated phenotypic traits have been mostly lost. The observed differences between the estimated continental genetic contribution proportions based on autosomal DIPs and X-DIPs reflect the effects of autosome and X-chromosome transmission behaviour and their different recombination patterns. This work shows the ability of the tested DIP panels to infer ancestry and confirm mating bias. To the best of our knowledge, this is the first study focusing on ancestry-informative autosomal DIP and X-DIP comparisons performed in a sample representing the entire Argentinean population.


Asunto(s)
Cromosomas Humanos Y/genética , Grupos Étnicos/genética , Polimorfismo Genético/genética , Grupo de Ascendencia Continental Africana/genética , Argentina , Grupo de Ascendencia Continental Europea/genética , Femenino , Genética de Población/métodos , Humanos , Masculino
8.
Am J Phys Anthropol ; 174(4): 701-713, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33539553

RESUMEN

Previous studies show that the indigenous people of the southern Cape of South Africa were dramatically impacted by the arrival of European colonists starting ~400 years ago and their descendants are today mixed with Europeans and Asians. To gain insight on the occupants of the Vaalkrans Shelter located at the southernmost tip of Africa, we investigated the genetic make-up of an individual who lived there about 200 years ago. We further contextualize the genetic ancestry of this individual among prehistoric and current groups. From a hair sample excavated at the shelter, which was indirectly dated to about 200 years old, we sequenced the genome (1.01 times coverage) of a Later Stone Age individual. We analyzed the Vaalkrans genome together with genetic data from 10 ancient (pre-colonial) individuals from southern Africa spanning the last 2000 years. We show that the individual from Vaalkrans was a man who traced ~80% of his ancestry to local southern San hunter-gatherers and ~20% to a mixed East African-Eurasian source. This genetic make-up is similar to modern-day Khoekhoe individuals from the Northern Cape Province (South Africa) and Namibia, but in the southern Cape, the Vaalkrans man's descendants have likely been assimilated into mixed-ancestry "Coloured" groups. The Vaalkrans man's genome reveals that Khoekhoe pastoralist groups/individuals lived in the southern Cape as late as 200 years ago, without mixing with non-African colonists or Bantu-speaking farmers. Our findings are also consistent with the model of a Holocene pastoralist migration, originating in Eastern Africa, shaping the genomic landscape of historic and current southern African populations.


Asunto(s)
Grupo de Ascendencia Continental Africana/genética , Grupos Étnicos/genética , Genética de Población/métodos , Cabello/química , Grupo de Ascendencia Continental Africana/historia , Antropología Física , Grupos Étnicos/historia , Genoma Humano/genética , Historia del Siglo XIX , Historia Antigua , Migración Humana/historia , Humanos , Polimorfismo de Nucleótido Simple/genética , Sudáfrica
9.
Am J Phys Anthropol ; 174(4): 686-700, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33555039

RESUMEN

OBJECTIVES: The aim of this research was to explore the origin, diversification, and demographic history of O1a-M119 over the past 10,000 years, as well as its role during the formation of East Asian and Southeast Asian populations, particularly the Han, Tai-Kadai-speaking, and Austronesian-speaking populations. MATERIALS AND METHODS: Y-chromosome sequences (n = 141) of the O1a-M119 lineage, including 17 newly generated in this study, were used to reconstruct a revised phylogenetic tree with age estimates, and identify sub-lineages. The geographic distribution of 12 O1a-M119 sub-lineages was summarized, based on 7325 O1a-M119 individuals identified among 60,009 Chinese males. RESULTS: A revised phylogenetic tree, age estimation, and distribution maps indicated continuous expansion of haplogroup O1a-M119 over the past 10,000 years, and differences in demographic history across geographic regions. We propose several sub-lineages of O1a-M119 as founding paternal lineages of Han, Tai-Kadai-speaking, and Austronesian-speaking populations. The sharing of several young O1a-M119 sub-lineages with expansion times less than 6000 years between these three population groups supports a partial common ancestry for them in the Neolithic Age; however, the paternal genetic divergence pattern is much more complex than previous hypotheses based on ethnology, archeology, and linguistics. DISCUSSION: Our analyses contribute to a better understanding of the demographic history of O1a-M119 sub-lineages over the past 10,000 years during the emergence of Han, Austronesians, Tai-Kadai-speaking populations. The data described in this study will assist in understanding of the history of Han, Tai-Kadai-speaking, and Austronesian-speaking populations from ethnology, archeology, and linguistic perspectives in the future.


Asunto(s)
Grupo de Ascendencia Continental Asiática/genética , Cromosomas Humanos Y/genética , Grupos Étnicos/genética , Genética de Población/métodos , Haplotipos/genética , Antropología Física , Grupo de Ascendencia Continental Asiática/clasificación , China , Grupos Étnicos/clasificación , Humanos , Masculino
10.
Hum Biol ; 92(2): 81-92, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33639639

RESUMEN

Six blood groups (Rh, MN, Duffy, Kidd, Kell, and Lutheran) were investigated among three major ethnic groups (Bosniaks, Bosnian Croats, and Bosnian Serbs), as well as 10 regional subpopulations across Bosnia and Herzegovina (B&H): Krajina; Posavina; northeastern, eastern, middle, and central Bosnia; Sarajevo region; eastern, central, and western Herzegovina. This is the first study that introduces the molecular genetic typing of five blood groups within the B&H population, with the exception of the RhD blood group. The sample consisted of 450 buccal swabs from unrelated individuals. Five blood group systems (RhD, RhC, RhE, Kidd, MN) were genotyped by PCR with sequence specific primers, while three blood group systems (Kell, Duffy, Lutheran) were genotyped by the PCR-restriction-fragment-length polymorphism method. Minor variation of genetic diversity was observed within the three major B&H ethnic groups, as well as within the 10 subpopulations stratified according to geographical criteria. No genetic differentiation among ethnic groups was noticed. These results are in agreement with the results of previous studies based on different molecular genetics markers, which indicate that the three B&H ethnic groups belong to the same gene pool. A similar level of genetic variance was observed within regional subpopulations, with no significant genetic differentiation among them. Comparison of intrapopulation genetic diversity of the B&H population with other European and non-European populations, based on three loci (RHD, MN, and KEL), clearly show that the level of genetic diversity of the B&H population is within the European range.


Asunto(s)
Antígenos de Grupos Sanguíneos , Protestantismo , Bosnia y Herzegovina , Grupos Étnicos/genética , Frecuencia de los Genes , Genotipo , Humanos
11.
Hum Biol ; 92(2): 115-127, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33639641

RESUMEN

Manipur, one of the northeastern states of India, lies on the ancient silk route and serves as a meeting point between Southeast Asia and South Asia. The origin and migration histories of Naga and Kuki tribal populations are not clearly understood. Moreover, Kukis have been traced to two different ancestries, which has created confusion among the people. The present study examined genomic affinities and differentiation of the Naga and Kuki tribal populations of Manipur, Northeast India. Twenty autosomal markers (8 Alu insertion-deletions, 12 restriction-fragment-length polymorphisms) were analyzed. Findings show genetic differences between Naga and Kuki tribal populations with respect to the allele distribution pattern, which was substantiated by genetic differentiation (GST = 5.2%) and molecular variance (AMOVA), where the highest percentage of among-group variances was observed between Naga and Kuki tribal groups (7.09%). However, genetic similarities with respect to allele distribution patterns in most of the loci were seen among their respective groups (Rongmei and Inpui, Thadou and Vaiphei). Rongmei and Inpui tribal populations (Naga group) belong to the Naga-Bodo linguistic group, and Thadou and Vaiphei (Kuki group) belong to the Northern Kuki-Chin linguistic group, suggesting that genetic similarities may not be independent of linguistic affinities. Despite differential genetic affinities, both Naga and Kuki tribal populations in Manipur show more proximity with Southeast Asian populations and Northeast Indian populations than with other Indian populations and global populations taken for comparison.


Asunto(s)
Grupo de Ascendencia Continental Asiática , Genómica , Asia , Grupo de Ascendencia Continental Asiática/genética , Grupos Étnicos/genética , Frecuencia de los Genes , Variación Genética/genética , Genética de Población , Humanos , India
12.
Nat Commun ; 12(1): 1236, 2021 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-33623038

RESUMEN

Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10-180). Comparing the 80th/20th PHS2 percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.


Asunto(s)
Grupos Étnicos/genética , Herencia Multifactorial/genética , Neoplasias de la Próstata/genética , Anciano , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica , Autoinforme
13.
BMC Res Notes ; 14(1): 45, 2021 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-33541395

RESUMEN

OBJECTIVES: Kazakhstan is a Central Asian crossroad of European and Asian populations situated along the way of the Great Silk Way. The territory of Kazakhstan has historically been inhabited by nomadic tribes and today is the multi-ethnic country with the dominant Kazakh ethnic group. We sequenced and analyzed the whole-genomes of five ethnic healthy Kazakh individuals with high coverage using next-generation sequencing platform. This whole-genome sequence data of healthy Kazakh individuals can be a valuable reference for biomedical studies investigating disease associations and population-wide genomic studies of ethnically diverse Central Asian region. DATA DESCRIPTION: Blood samples have been collected from five ethnic healthy Kazakh individuals living in Kazakhstan. The genomic DNA was extracted from blood and sequenced. Sequencing was performed on Illumina HiSeq2000 next-generation sequencing platform. We sequenced and analyzed the whole-genomes of ethnic Kazakh individuals with the coverage ranging from 26 to 32X. Ranging from 98.85 to 99.58% base pairs were totally mapped and aligned on the human reference genome GRCh37 hg19. Het/Hom and Ts/Tv ratios for each whole genome ranged from 1.35 to 1.49 and from 2.07 to 2.08, respectively. Sequencing data are available in the National Center for Biotechnology Information SRA database under the accession number PRJNA374772.


Asunto(s)
Grupo de Ascendencia Continental Asiática , Genoma Humano , Grupo de Ascendencia Continental Asiática/genética , Grupos Étnicos/genética , Humanos , Kazajstán , Secuenciación Completa del Genoma
14.
Gene ; 777: 145466, 2021 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-33524518

RESUMEN

The dopamine - related genes, like dopamine D2 receptor (DRD2) gene and ankyrin repeat and kinase domain containing 1 (ANKK1) gene are implicated in neurological functions. Some polymorphisms of the DRD2/ANKK1 locus (TaqIA, TaqIB, TaqID) have been used to study genetic diversity and the evolution of human populations. The present investigation aims to assess the genetic diversity in seven North African populations in order to explore their genetic structure and to compare them to others worldwide populations studied for the same locus. Nine single nucleotide polymorphisms (SNPs) from the DRD2/ANKK1 locus (rs1800497 TaqIA, rs2242592, rs1124492, rs6277, rs6275, rs1079727, rs2002453, rs2234690 and rs1079597 TaqIB) were typed in 366 individuals from seven North African populations: six from Tunisia (Sousse, Smar, Kesra, Kairouan, Mehdia and Kerkennah) and one from Libya. The allelic frequencies of rs2002453 and rs2234690 were higher in the Smar population than in the other North African populations. More, the Smar population showed the lowest average heterozygosity (0.313). The principal component analysis (PCA) showed that the Smar population was clearly separated from others. Furthermore, linkage disequilibrium analysis shown a high linkage disequilibrium in the North African population and essentially in Smar population. Comparison with other world populations has shown that the heterozygosity of North African population was very close to that of the African and European populations. The PCA and the haplotypic analysis suggested the presence of an important Eurasian genetic component for the North African population. These results suggested that the Smar population was isolated from the others North Africans ones by its peculiar genetic structure because of isolation, endogamy and genetic drift. On the other hand, the North African population is characterized by a multi ancestral gene pool from Eurasia and sub-Saharan Africa due to human migration since prehistoric times.


Asunto(s)
Proteínas Serina-Treonina Quinasas/genética , Receptores de Dopamina D2/genética , Adulto , África del Norte/etnología , Grupo de Ascendencia Continental Africana , Alelos , Grupos Étnicos/genética , Femenino , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad/genética , Variación Genética/genética , Genómica , Genotipo , Técnicas de Genotipaje , Haplotipos/genética , Heterocigoto , Migración Humana , Humanos , Desequilibrio de Ligamiento/genética , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética
17.
Nucleic Acids Res ; 49(2): 1075-1093, 2021 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-33398350

RESUMEN

Defects in the posttranscriptional modifications of mitochondrial tRNAs have been linked to human diseases, but their pathophysiology remains elusive. In this report, we investigated the molecular mechanism underlying a deafness-associated tRNAIle 4295A>G mutation affecting a highly conserved adenosine at position 37, 3' adjacent to the tRNA's anticodon. Primer extension and methylation activity assays revealed that the m.4295A>G mutation introduced a tRNA methyltransferase 5 (TRMT5)-catalyzed m1G37 modification of tRNAIle. Molecular dynamics simulations suggested that the m.4295A>G mutation affected tRNAIle structure and function, supported by increased melting temperature, conformational changes and instability of mutated tRNA. An in vitro processing experiment revealed that the m.4295A>G mutation reduced the 5' end processing efficiency of tRNAIle precursors, catalyzed by RNase P. We demonstrated that cybrid cell lines carrying the m.4295A>G mutation exhibited significant alterations in aminoacylation and steady-state levels of tRNAIle. The aberrant tRNA metabolism resulted in the impairment of mitochondrial translation, respiratory deficiency, decreasing membrane potentials and ATP production, increasing production of reactive oxygen species and promoting autophagy. These demonstrated the pleiotropic effects of m.4295A>G mutation on tRNAIle and mitochondrial functions. Our findings highlighted the essential role of deficient posttranscriptional modifications in the structure and function of tRNA and their pathogenic consequence of deafness.


Asunto(s)
Pérdida Auditiva Sensorineural/genética , Mutación Puntual , ARN de Transferencia de Isoleucina/genética , Adenosina Trifosfato/biosíntesis , Adulto , Proteínas Arqueales/metabolismo , Autofagia , Secuencia de Bases , Línea Celular , ADN Mitocondrial/genética , Grupos Étnicos/genética , Femenino , Pleiotropía Genética , Pérdida Auditiva Sensorineural/etnología , Humanos , Isoleucina/metabolismo , Masculino , Herencia Materna , Potencial de la Membrana Mitocondrial , Methanocaldococcus/enzimología , Metilación , Persona de Mediana Edad , Mitocondrias/metabolismo , Simulación de Dinámica Molecular , Conformación de Ácido Nucleico , Fosforilación Oxidativa , Linaje , Biosíntesis de Proteínas , Procesamiento Postranscripcional del ARN , Proteínas Recombinantes/metabolismo , Aminoacilación de ARN de Transferencia , Adulto Joven , ARNt Metiltransferasas/metabolismo
18.
Medicine (Baltimore) ; 100(2): e24137, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33466187

RESUMEN

ABSTRACT: To provide information and a basis for improved hepatitis C prevention and treatment, we aimed to determine the distribution of hepatitis C virus (HCV) genotypes among patients with hepatitis C from 4 ethnic minorities in Liaoning Province of China over the past 8 years and analyze and explore the virus' genotype evolution and possible clinical significance.For gene-sequencing, we collected peripheral blood samples of HCV-infected patients belonging to the Korean, Hui, Mongol, and Manchu ethnic minorities in Liaoning Province who were diagnosed at the Second Hospital of Dalian Medical University, Anshan Central Hospital, and the Second People's Hospital of Fuxin City between November 2011 and November 2019. To analyze genotype evolution and possible influencing factors, we determined the ratio of various genotypes. Among the 102 HCV-infected patients from 4 ethnic minorities in Liaoning Province, 46 had gene typing (GT)1b (45.10%), 15 had GT2a (14.71%), 14 had GT3a (13.73%), 13 had GT6a (12.75%), 3 had GT1a (2.94%), and 11 had an unclassified genotype (10.78%). The distribution of various genotypes in the Korean, Mongol, and Manchu ethnic minorities was significantly different (χ2 = 10.788, P = .029; χ2 = 7.846, P = .049; and χ2 = 22.400, P = .000, respectively). All ethnic minorities exhibited >40% of GT1b. In the Korean (14/33) and Manchu (14/30) ethnic minorities, the proportion of GT1b was significantly higher than those of other genotypes (P < .05). The ethnic Koreans had a high proportion of GT3a (18.18%, 6/33), whereas the ethnic Mongolians had a high proportion of GT6a (23.08%, 6/26). GT1a was only found in the Korean (6.06%, 2/33) and Manchu (3.33%, 1/30) ethnic minorities; in the Hui ethnic minority, only 3 genotypes were prevalent: GT1b, GT2, and GT3a. The ethnic minorities in Liaoning Province currently have diverse HCV genotypes; the most prevalent genotype is GT1b, followed by GT2a and GT3a, and the prevalence of GT3 and GT6 has increased. The distribution of HCV genotypes varies across different ethnic minorities. The Korean and Manchu ethnic minorities have the most prevalent genotypes, whereas the Hui ethnic minority has a relatively single distribution of the HCV genotype.


Asunto(s)
Grupos Étnicos/genética , Genotipo , Hepacivirus/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , China/etnología , Grupos Étnicos/estadística & datos numéricos , Femenino , Hepatitis C/etnología , Hepatitis C/genética , Hepatitis C/virología , Humanos , Masculino , Persona de Mediana Edad
19.
Cancer Sci ; 112(3): 1300-1309, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33426772

RESUMEN

Genetic alterations in adult T-cell leukemia/lymphoma (ATLL), a T-cell malignancy associated with HTLV-1, and their clinical impacts, especially from the perspective of viral strains, are not fully elucidated. We employed targeted next-generation sequencing and single nucleotide polymorphism array for 89 patients with ATLL in Okinawa, the southernmost islands in Japan, where the frequency of HTLV-1 tax subgroup-A (HTLV-1-taxA) is notably higher than that in mainland Japan, where most ATLL cases have HTLV-1-taxB, and compared the results with previously reported genomic landscapes of ATLL in mainland Japan and the USA. Okinawan patients exhibited similar mutation profiles to mainland Japanese patients, with frequent alterations in TCR/NF-ĸB (eg, PRKCB, PLCG1, and CARD11) and T-cell trafficking pathways (CCR4 and CCR7), in contrast with North American patients who exhibited a predominance of epigenome-associated gene mutations. Some mutations, especially GATA3 and RHOA, were detected more frequently in Okinawan patients than in mainland Japanese patients. Compared to HTLV-1-taxB, HTLV-1-taxA was significantly dominant in Okinawan patients with these mutations (GATA3, 34.1% vs 14.6%, P = .044; RHOA, 24.4% vs 6.3%, P = .032), suggesting the contribution of viral strains to these mutation frequencies. From a clinical viewpoint, we identified a significant negative impact of biallelic inactivation of PRDM1 (P = .027) in addition to the previously reported PRKCB mutations, indicating the importance of integrated genetic analysis. This study suggests that heterogeneous genetic abnormalities in ATLL depend on the viral strain as well as on the ethnic background. This warrants the need to develop therapeutic interventions considering regional characteristics.


Asunto(s)
Biomarcadores de Tumor/genética , Perfil Genético , Infecciones por HTLV-I/genética , Virus Linfotrópico T Tipo 1 Humano/genética , Leucemia-Linfoma de Células T del Adulto/genética , Adulto , Anciano , Anciano de 80 o más Años , Variaciones en el Número de Copia de ADN , Grupos Étnicos/genética , Femenino , Estudios de Seguimiento , Productos del Gen tax/genética , Técnicas de Genotipaje , Infecciones por HTLV-I/patología , Infecciones por HTLV-I/virología , Secuenciación de Nucleótidos de Alto Rendimiento , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Humanos , Japón , Estimación de Kaplan-Meier , Leucemia-Linfoma de Células T del Adulto/mortalidad , Leucemia-Linfoma de Células T del Adulto/patología , Leucemia-Linfoma de Células T del Adulto/virología , Masculino , Persona de Mediana Edad , Mutación , Polimorfismo de Nucleótido Simple , Pronóstico
20.
Forensic Sci Int ; 318: 110637, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33309992

RESUMEN

Sudden cardiac death (SCD) has become a global problem due to its high mortality in the general population. Identification of genetic factors predisposed to SCD is significant since it enables genetic testing that would contribute to molecular diagnosis and risk stratification of SCD. It has been reported that HSPA1B gene mutations might be related with SCD. In this study, based on candidate-gene-based approach and systematic screening strategy, a 5-base pair insertion/deletion (Indel) polymorphism (rs3036297) in the 3'UTR of HSPA1B gene was selected to perform a case-control study aiming to investigate its association with SCD susceptibility in Chinese populations. Logistic regression analysis showed that the insertion allele of rs3036297 was correlated with a comparatively lower risk for SCD [OR=0.58, 95%CI=0.43-0.77, P=1.28×10-4] compared with the deletion allele. Luciferase activity assay indicated that HSPA1B expression could be regulated by rs3036297 through interfering binding with miR-134-5p. Furthermore, analysis of database from Haploreg and GTEx revealed that the rs3036297 variant was involved in potential cis-regulatory element with the promoter of HLA-DRB5 through a long-range interaction and the deletion allele of rs3036297 increased HLA-DRB5 expression. In conclusion, the rs3036297 variant may regulate HSPA1B expression via a mechanism of miRNA binding and HLA-DRB5 expression via a long-range promoter interaction through which contributed to SCD susceptibility. Therefore, rs3036297 would be a potential marker for molecular diagnosis and genetic counseling of SCD.


Asunto(s)
Muerte Súbita Cardíaca/etiología , Predisposición Genética a la Enfermedad , Proteínas HSP70 de Choque Térmico/genética , Mutación INDEL , Polimorfismo Genético , Grupo de Ascendencia Continental Asiática/genética , Sitios de Unión , Estudios de Casos y Controles , China , Grupos Étnicos/genética , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Humanos , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad
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