HLA class I in three West African ethnic groups: genetic distances from sub-Saharan and Caucasoid populations

Fulani of Burkina Faso (West Africa) are a particularly interesting ethnic group because of their lower susceptibility to Plasmodium falciparum malaria as compared to sympatric populations, Mossi and Rimaibé. Moreover, the occurrence of a Caucasoid component in their genetic make-up has been suggested on the basis of their physical traits and cultural traditions even though this view was not supported by genetic studies. A total of 149 unrelated subjects (53 Mossi, 47 Rimaibé and 49 Fulani) have been typed for 97 HLA class I alleles with the amplification refractory mutation system/polymerase chain reaction (ARMS/PCR) technique. Mossi and Rimaibé data were pooled since none of the 42 statistically testable alleles exhibited a significant heterogeneity. These pooled gene frequencies were found to be very different from those of Fulani: a certain (P<0.001) or a likely (0.001 相似文献   

Allele-specific PCR and Next-generation sequencing based genetic screening for Congenital Adrenal Hyperplasia in India

Genetic screening of Congenital Adrenal Hyperplasia (CAH) is known to be challenging due to the complexities in CYP21A2 genotyping and has not been the first-tier diagnostic tool in routine clinical practice. Also, with the advent of massive parallel sequencing technology, there is a need for investigating its utility in screening extended panel of genes implicated in CAH. In this study, we have established and utilized an Allele-Specific Polymerase Chain Reaction (ASPCR) based approach for screening eight common mutations in CYP21A2 gene followed by targeted Next Generation Sequencing (NGS) of CYP21A2, CYP11B1, CYP17A1, POR, and CYP19A1 genes in 72 clinically diagnosed CAH subjects from India. Through these investigations, 88.7% of the subjects with 21 hydroxylase deficiency were positive for eight CYP21A2 mutations with ASPCR. The targeted NGS assay was sensitive to pick up all the mutations identified by ASPCR. Utilizing NGS in subjects negative for ASPCR, five study subjects were homozygous positive for other CYP21A2 variants: one with a novel c.1274G>T, three with c.1451G>C and one with c.143A>G variant. One subject was compound heterozygous for c.955C>T and c.1042G>A variants identified using ASPCR and NGS. One subject suspected for a Simple Virilizing (SV) 21 hydroxylase deficiency was positive for a CYP19A1:c.1142A>T variant. CYP11B1 variants (c.1201-1G>A, c.1200+1del, c.412C>T, c.1024C>T, c.1012dup, c.623G>A) were identified in all six subjects suspected for 11 beta-hydroxylase deficiency. The overall mutation positivity was 97.2%. Our results suggest that ASPCR followed by targeted NGS is a cost-effective and comprehensive strategy for screening common CYP21A2 mutations and the CAH panel of genes in a clinical setting.     

Review of the mutagenicity of ethylene oxide

Ethylene oxide has been shown to be an effective mutagen in a variety of organisms ranging from bacteria to mammalian cells. There is also an association between ethylene oxide exposure and human somatic cell cytogenetic damage. Furthermore, ethylene oxide has been shown to alkylate protein and DNA at exposure levels that have been encountered occupationally. Ethylene oxide is not only effective at producing somatic cell mutations but also at inducing genetic damage in germ cells. While it is clear that ethylene oxide is a germ cell mutagen in whole mammals, the mechanism(s) by which it produces genetic lesions in germ cells is uncertain.     

The ancestry of spondyloepimetaphyseal dysplasia with joint laxity (SEMDJL) in South Africa

Comprehensive genealogical investigations have been undertaken in eight families in the Afrikaans-speaking community of South Africa, in which at least one person had spondyloepimetaphyseal dysplasia with joint laxity (SEMDJL). All eight families had ancestral links with two females. These women had multiple marriages and cohabitations during the late 17th and early 18th centuries and they were 12 generations removed from the affected individuals. The identification of these common progenitors confirmed the syndromic homogeneity of SEMDJL in South Africa and permitted recognition of numerous obligate heterozygotes, thus facilitating biomolecular investigations of the basic defect.     

华南、华北人群HLA-DQB1等位基因多态性

目的从基因水平调查了中国华南、华北地区人群HLA-DQB1等位基因频率，并研究比较两地区人群HLA-DQB1多态性分布。方法采用深圳益生堂生物企业有限公司研制开发的“HLA-DQB1低分辨率分型基因芯片检测试剂盒”，应用聚合酶链反应．序列特异性引物＋序列特异性寡核苷酸探针芯片检测技术，对700名南方地区的中国人和320名北方地区的中国人进行基因分型。结果鉴定了10个HLA-DQB1等位基因，获得了一组准确、科学的统计数据。结论得到了中国华南、华北地区人群HLA-DQB1等位基因频率差异的数据，证明中国人群HLA-DQB1＊02，05，0601，0602，0603的分布南北差异有统计学意义（P〈0．05），为疾病相关性研究、人文科学研究提供了可靠的遗传学数据。     

Mechanisms of action of major-histocompatibility-complex-linked genes affecting reproduction

PROBLEM: To provide insight into the mechanisms of action of the major-histocompatibility-complex (MHC)-linked genes affecting reproduction. METHOD OF STUDY: The data were obtained using a variety of cellular and molecular techniques in experimental animals and from population genetic studies in humans. RESULTS: In the mouse, the preimplantation embryonic development (Ped) locus, whose functional gene is Q9, regulates fast and slow cleavage of the early embryo. There is also evidence for a growth and reproduction complex (Grc)-like region from serologic, molecular, and cytogenetic studies. In the human, the human leukocyte antigen (HLA)-G gene has been associated with an increased rate of embryonic cleavage in those embryos that express the HLA-G antigen. Sharing of HLA antigens in couples has been associated with recurrent spontaneous abortions, gestational trophoblastic tumors, and unexplained infertility. Detailed mapping studies showed that the genes responsible are not the HLA genes themselves, but genes closely linked to the HLA-DR-DQ-B genes. The HLA region genes can interact epistatically with the C3 allele of transferrin to increase the incidence of fetal loss. In the rat, the Grc region, which is closely linked to the MHC, has been associated with embryonic loss, growth defects, and susceptibility to chemical carcinogens. The Grc can interact epistatically with the tail anomaly lethal (Tal) gene or the hood restriction (Hre) gene to enhance these effects. CONCLUSIONS: There are two basic mechanisms for the effects of MHC-linked genes on reproduction and development: individual gene effects (Ped [Q9], HLA-G) and extended genetic effects (MHC-linked genes in the rat [Grc] and in the human). The nature of these genetic effects, particularly the MHC-linked effects, can also provide some insight into the different theories of human origins: These effects are most consistent with the monogenic theory.     

Mental retardation,macrocephaly, short stature and craniofacial dysmorphism in three sisters: A new entity among the mental retardation-macrocephaly syndromes?

In this report we describe a true macrocephaly-mental retardation syndrome in three sisters. In addition, they present a distinct craniofacial dysmorphism with coarse facial features. Further family investigation revealed a similar macrocephaly in the mother and her father, suggesting autosomal dominant transmission of this familial macrocephaly. Present knowledge of the nosology of the mental retardation-macrocephaly association is reviewed and discussed.     

Will the new cytogenetics replace the old cytogenetics?

With the advent of array-based comparative genomic hybridization technology, the analog cytogenetic analysis that has been used for the past 100 years could be replaced by the quantitative, microarray-based molecular analysis. Major advantages of the new array-based cytogenetic technologies are the high resolution and the high throughput. This technology is the first to offer an autonomous whole-chromosome analysis in one hybridization reaction for the detection of submicroscopic gains/losses. However, as with any new technology, it needs to be validated with regard to its performance in various applications (e.g. clinical genetic testing and cancer applications), comparative cost, and the data interpretation.     

Epidemiologic survey and genetic analysis of endemic hepatitis C virus infection in a Japanese town with a high prevalence of hepatitis B virus carriers

Mass screening for hepatitis C virus antibody was carried out in 875 inhabitants (313 men and 562 women) of a town in Japan with a high rate of hepatitis B virus infection. The overall rate of positivity for anti-HCV was 8.8% (6.4% in men and 10,1% in women). The rate of positivity for hepatitis B virus surface antigen was 11.2%. Five subjects (0.6%) were positive for both markers. HCV-RNA was detected in 65 (88.4%) of 77 individuals who were positive for anti-HCV and in 1 (1.5%) of 60 individuals negative for anti-HCV. The genotype of the HCV genome was determined by PCR analysis using type-specific primers in 60 individuals. HCV type 1b was detected in 51 subjects (85%), type 2a in 3 subjects (5%), and type 2b in 6 subjects (10%). None of the individuals was infected with more than one genotype. The nucleotide sequences of the partial nonstructural 5 region of HCV type 1b genotype obtained from 6 individuals showed at least 92.0% homology in the nucleotide sequence, and 94.8% homology in the amino acid sequence. Homology among these clones was greater than their homology with previously described type 1 b sequences. The findings suggest that there was a specific local origin of HCV infection, although it was not possible to identify any single source of HCV infection. The results also indicate the presence of asymptomatic HCV carriers. © 1995 Wiley-Liss, Inc.