Using linked markers to infer the age of a mutation

Advances in sequencing and genotyping technologies over the last decade have enabled geneticists to easily characterize genetic variation at the nucleotide level. Hundreds of genes harboring mutations associated with genetic disease have now been identified by positional cloning. Using variation at closely linked genetic markers, it is possible to predict the times in the past at which particular mutations arose. Such studies suggest that many of the rare mutations underlying human genetic disorders are relatively young. Studies of variation at genetic markers linked to particular mutations can provide insights into human geographic history, and historical patterns of natural selection and disease, that are not available from other sources. We review two approaches for estimating allele age using variation at linked genetic markers. A phylogenetic approach aims to reconstruct the gene tree underlying a sample of chromosomes carrying a particular mutation, obtaining a “direct” estimate of allele age from the age of the root of this tree. A population genetic approach relies on models of demography, mutation, and/or recombination to estimate allele age without explicitly reconstructing the gene tree. Phylogenetic methods are best suited for studies of ancient mutations, while population genetic methods are better suited for studies of recent mutations. Methods that rely on recombination to infer the ages of alleles can be fine‐tuned by choosing linked markers at optimal map distances to maximize the information available about allele age. A limitation of methods that rely on recombination is the frequent lack of a fine‐scale linkage map. Maximum likelihood and Bayesian methods for estimating allele age that rely on intensive numerical computation are described, as well as “composite” likelihood and moment‐based methods that lead to simple estimators. The former provide more accurate estimates (particularly for large samples of chromosomes) and should be employed if computationally practical. Hum Mutat 18:87–100, 2001. © 2001 Wiley‐Liss, Inc.     

青岛地区D6S477等五个短串联重复序列基因座的遗传多态性研究

目的 了解D6S477等5个基因座在青岛地区汉族群体中基因型分布及等位基因频率等遗传多态性数据，初步探讨其应用价值。方法 收集200名青岛地区汉族无关个体的静脉血，ACD抗凝，采用Chelex法提取DNA，应用聚合酶链反应技术，扩增D6S477、D9S1118、D18S865、D19S400和D20S161基因座的短串联重复序列，聚丙烯酰胺凝胶垂直电泳，银染显色分型。结果 获得了青岛地区汉族群体上述5个基因座的等位基因频率，基因型分布均符合Hardy-Weinberg平衡（P〉0．05）。结论 这5个基因座在青岛地区汉族群体中有较高的非父排除率和个人识别机率，在遗传学研究中有较高的应用价值。     

Genetic markers in the Tuvan population of Todja, Siberia

Todja is a secluded region of northern Tuva situated in the Sayany Mountains, Siberia. The aboriginal population of Todja is Tuvan. A total of 128 healthy Tuvans living in Todja were typed for HLA-A, -B and -C antigens and several plasma and erythrocyte protein polymorphisms (Hp, Tf, Gc, ESD, ACP, PGM1, PGD and ADA). The observed frequencies of all 8 blood protein and HLA genotypes were in agreement with Hardy-Weinberg expectations. The most frequent HLA antigens in Todjans are A2 (0.36). A3 (0,24), A9 (0.50), B15 (0.34) and B40 (0.50). HLA haplotypes A2B5, A2B40, A9B15 and A9B40 are most common in this population. The observed frequencies of protein polymorphisms and HLA antigens and haplotypes in Todjans are similar to those of other Mongoloid populations. A comparison of HLA frequencies currently observed in Todjans with those obtained 20 years ago at the same locality showed minor changes attributable to the effect of migration.     

Can subjects with a positive allergen skin test be selected by a short questionnaire?

The objective was to evaluate a postal questionnaire screening procedure for selection of subjects with positive reactions to skin prick tests with common allergens. The project consisted of a screening, with subsequent skin prick test of two selected groups. The setting was the Glostrup Population Studies institute in Copenhagen, Denmark. Participants in the screening included 8000 subjects, aged 15–69 years. The subjects were randomly selected from the population of western Copenhagen County, Denmark. From the 6998 respondents (87.5%), 793 subjects were randomly selected (Random Group), and 788 subjects were chosen on the basis of their answers to the questionnaire (Symptom Group). Both groups were invited to take skin prick tests. Attendance rates were 75.5% (Random Group) and 80.6% (Symptom Group).
The main outcome measures were responses (yes or no) to the specific questions and the subjects' skin reaction (positive or negative). The association between symptoms and skin reactivity, adjusted for the effects of sex and age, was summarized by odds ratios. Symptoms on exposure to allergens were highly associated with positive skin reactivity. In the Symptom Group the percentage of subjects with at least one positive skin reaction was 57.7%, which was twice as much (28.4%) as in the Random Group. The results show that it was possible to select a group with high skin reactivity on the basis of the symptoms reported in the screening. Questions about exposure to allergens were the most appropriate for selection of this group.     

我国福建汉族人HSP70基因多态性分析

目的了解福建省汉族人HSP70基因多态性分布，进而为探讨HSP70基因多态性与疾病的相关性提供遗传背景资料。方法应用聚合酶链反应技术、限制性内切酶分析检测了127名福建汉族正常人的HSP70基因3个多态性位点，并比较了部分不同地区和人群之间的基因型与等位基因频率。结果福建汉族人HSP70-1基因型（GG，GC和CC）分布频率分别是55．1％、40．2％和4．7％；HSP70-2基因型（从，AG和GG）分布频率分别是44．1％、铝．8％和6．9％；HSP70-hom基因型（Tr，TC和CC）分布频率分别是59.8％、37．0％和3．2％；HSP70-1等位基因频率G和C分别是75．2％和24．8％；HSP70-2等位基因频率A和G分别是68．5％和31．5％；HSP70-hom等位基因频率T和C分别是78．3％和21．7％。福建汉族人HSP70-1的基因型分布和等位基因频率同日本、墨西哥人群比较差异无统计学意义，与美国和西班牙人比较，差异有统计学意义（P〈0．01）。福建汉族人HSP70-1的GG纯合型（55．1％）显著高于美国（42．6％）和西班牙（33．0％）人群；福建汉族人HSP70-2的基因型分布和等位基因频率与日本人比较差异无统计学意义，与墨西哥、美国和西班牙人群比较，差异有统计学意义（P〈0．05），福建汉族人HSP70-2的AA纯合型（44．1％）高于墨西哥（23．O％）、美国（38．8％）和西班牙（20．O％）人群；福建汉族人群的HSP70-hom基因型和等位基因频率分布同日本、墨西哥、美国和西班牙人群的基本一致，差异无统计学意义，福建汉族人群的HSP70基因型和等位基因频率分布同中国台湾汉族人基本一致，差异无统计学意义，与武汉地区汉族人某些位点存在差异。结论福建汉族人HSP70基因多态性分布不同于某些地区的人群，具有种族和地区差异。     

藏汉民族线粒体基因组全序列的比较研究

目的 以藏汉民族线粒体基因组全序列为基础,进行Haplogroup构建和系统发生分析,在全序列水平上比较核苷酸的变异,阐释可能的变异机制和蕴含的生物学意义.方法 采用Applied Biosystems 3730DNA自动测序仪分别对40名藏族和50名汉族的标本进行线粒体DNA序列测定,应用phredPhrap 16.0软件进行全序列拼接,并以rCRS(revised Cambridge Reference Sequence)为标准与测定序列进行比对分析;根据MTTO-MAP的标准,通过Network方法进行Haplogroup构建和系统发生的分析,并结合其它方法对产生的数据进行深入解读.结果 数据分析结果显示:在系统发生上,藏汉民族90个线粒体DNA序列归类到13个Haplogroups,除M9以外,其它各Haplogroup出现频率之间比较差异无统计学意义;通过两个民族的线粒体DNA全序列比对,发现21个分布频率有统计学意义的变异位点,其中的5个为新变异位点;另外,对D-Loop区的5个突变位点进行了单倍型构建,90个标本可分为2种Supertype,发现在藏汉民族之间Supertypel和Supertype 2的分布频率均有统计学意义.结论 藏汉民族在种族起源和系统发生上具有较近的母系遗传关系;在全序列有统计学意义的位点究竟是适应性或者中性选择,抑或是一种病理性突变尚需深入的探讨.     

Fear of Movement/Injury in the General Population: Factor Structure and Psychometric Properties of an Adapted Version of the Tampa Scale for Kinesiophobia

In recent years, several studies have pointed out the importance of pain-related fear in the development and maintenance of chronic pain. An important instrument for measuring pain-related fear in the context of low back pain is the Tampa Scale for Kinesiophobia (TSK). Recently, a version of this questionnaire has been developed for administration among the general population (TSK-G). To determine the factor structure of the TSK-G, data from a random sample of the Dutch general population were studied separately for people who had had back complaints in the previous year, and people who had been without back complaints. For both groups the TSK-G appeared to consist of one, internally consistent, factor of 12 items. The one-factor TSK-G also appeared valid after comparison with scores on measures of catastrophizing and general health status.     

西北地区汉族人群HLA-A、-B、-DRB1基因座单倍型分析

目的 分析西北地区汉族群体HLA-A、-B和-DRB1基因座等位基因频率和HIA-A-B、B-DRB1和A-B-DRB1单倍型，获得单倍型频率数据。方法 采用序列特异性寡核苷酸探针反向斑点杂交技术对西北地区62个家系和101个无关个体HLA-A、-B和-DRB1基因座进行基因分型，分析HLA单倍型。结果 在西北地区汉族人群中检出15个HLA-A等位基因，28个HLA-B等位基因，13个HLA-DRB1等位基因，A02、A11、A24、B13、B15、1340、DRB1＊04、DRB1＊07、DRB1＊09和DRB1＊15基因频率较高（〉10％），A02（0．3244）、B13（0．1200）和DRB1＊15（0．1400）等位基因频率最高。分析得出HLA-A-B、B-DRB1、A-B-DRB1单倍型分别有122、147和278种，83种A-B-DRB1单倍型有至少两条以上相同的单倍型，占总单倍型数的18．44％（83／450）。A30-B13-DRB1＊07、A02-B46-DRB1＊09、A01-B37-DRB1＊10、A24-B15-DRB＊15、A02-B46-DRB1＊08、A33-B58-DRB1＊03是最常见的单倍型。结论 西北地区汉族群体HLA单倍型多态性较为丰富，等位基因频率和单倍型频率数据可用于骨髓移植供者的选择、法医学亲权鉴定以及人类学研究。     

Forensic characteristics and phylogenetic analysis of 23 Y-STR loci in the Miao population from Guizhou province,southwest China

Background: Investigation of haplotype/allele frequency data of Y-STR loci in ethnically diverse populations is essential for forensic reference database construction and genetic application. However, the population genetic characteristics of the Chinese Miao minority from Guizhou Province remain uncharacterised.

Aim: To assess forensic characteristics for 23 Y-Chromosomal STR loci in Guizhou Miao and explore population genetic relationships with geographically neighbouring populations.

Subjects and methods: Twenty-three Y-Chromosomal STRs were genotyped using the Powerplex^® Y23 system in 103 unrelated Chinese Miao males from Guizhou Province, southwest China. Haplotypes and forensic parameters were obtained. Population relationships of Guizhou Miao with others were revealed using AMOVA and an MDS plot.

Results: A total of 96 haplotypes were identified with overall haplotype diversity (HD) and discrimination capacity (DC) of 0.9985 and 0.9320, respectively. Genetic differentiation was observed with most of the comparison populations, prominently for Guizhou Shui.

Conclusion: The 23 Y-STR loci were highly polymorphic and discriminating in the Guizhou Miao population and could be used for forensic practice and population genetic studies. Population relationship analysis revealed Guizhou Miao had a close genetic relationship with geographically close Guizhou Gelao, as well as Han majorities derived from different regions.     

Genetic variations in five genes involved in the excitement of cardiomyocytes

We provide here 29 genetic variations, including 28 novel ones, in five genes that are potentially involved in the excitement of cardiomyocytes: we found 4 in KCNA10, 2 in KCNK1, 8 in KCNK6, 11 in SLC18A1 (VMAT1), and 4 in SLC6A2 (norepinephrine transporter). We also examined their allelic frequencies in a Japanese population of long QT syndrome-affected and nonaffected individuals. These data would be useful for genetic association studies designed to investigate acquired arrhythmias. Received: May 22, 2001 / Accepted: June 8, 2001