福建省两个汉族瘢痕疙瘩家系易感基因位点与染色体7p11的连锁分析

目的：探讨福建省两个汉族瘢痕疙瘩家系易感基因位点是否与7p11存在连锁关系。方法：从来自福建省2个汉族瘢痕疙瘩家系中选出26名具有较高遗传学研究意义的成员作为研究对象,采集他们的外周静脉血样,提取基因组DNA,参照国外最近相似研究的方法,在染色体7p11上选取已知的4个最大两点LOD值的微卫星为遗传标记,经PCR扩增,产物基因分型,再进行连锁分析。结果：在重组率Θ=0～0．1时,这些微卫星标记的两点LOD值都小于-2,排除这些标记与染色体7p11的连锁关系。结论：本研究发现福建省两个汉族瘢痕疙瘩家系的易感基因位点不在染色体7p11上的遗传学证据,说明瘢痕疙瘩易感基因位点存在异质性。     

中国人群瘢痕疙瘩家系与染色体 2q23 和 7p11 的连锁分析

目的探讨中国人群瘢痕疙瘩家系是否与2q23和7p11存在连锁关系。方法选择两个中国人群瘢痕疙瘩大家系,从中共选出51名成员,采集其外周静脉血样,提取基因组DNA;参照国外最近相似研究的文献报道,在染色体2q23和7p11上,分别选取6个和4个微卫星标记,经多重PCR扩增,产物片断基因分型,再进行连锁分析。结果在重组率θ=0时,这些微卫星标记的两点LOD值绝大部分都小于-2,排除连锁关系存在。结论本研究首次发现了中国人群瘢痕疙瘩家系的易感基因位点不在染色体2q23和7p11上的遗传学证据,说明瘢痕疙瘩易感基因位点存在异质性。     

中国人群瘢痕疙瘩家系与染色体 2q23 和 7p11 的连锁分析

目的 探讨中国人群瘢痕疙瘩家系是否与2q23和7p11存在连锁关系.方法 选择两个中国人群瘢痕疙瘩大家系,从中共选出51名成员,采集其外周静脉血样,提取基因组DNA;参照国外最近相似研究的文献报道,在染色体2q23和7p11上,分别选取6个和4个微卫星标记,经多重PCR扩增,产物片断基因分型,再进行连锁分析.结果 在重组率θ=0时,这些微卫星标记的两点LOD值绝大部分都小于-2,排除连锁关系存在.结论 本研究首次发现了中国人群瘢痕疙瘩家系的易感基因位点不在染色体2q23和7p11上的遗传学证据,说明瘢痕疙瘩易感基因位点存在异质性.     

中国汉族瘢痕疙瘩家系易感基因位点的定位分析研究

目的 定位中国汉族瘢痕疙瘩家系的易感基因位点.方法 采集2个4代发病的中国汉族瘢痕疙瘩大家系51例成员的外周静脉血样.提取基因组DNA;假定Fas基因为该家系致病基因的候选基因位点.选取位于10q23.31上Fas基因周围共约10Mbp范围内与细胞凋亡障碍有关的已知基因相邻的微卫星标记D10S1687、D10S1765、D10S1735和D10S1562,对这些微卫星位点进行PCR扩增,产物片断基因分型,再进行连锁分析.结果 在重组率θ=0～0.5时,这些微卫星标记的两点LOD值绝大部分都小于1,排除连锁关系存在.结论 研究发现中国汉族瘢痕疙瘩家系易感基因位点不在染色体10q23.31区域.     

一汉族瘢痕疙瘩家系的易感基因定位分析研究

目的采用连锁分析方法探讨瘢痕疙瘩(keloid)家系的疾病易感基因与15q22.31-q23及18q21.1区域的连锁关系。方法1个中国东北地区5代keloid家系,采集家系中32名成员的外周血标本提取DNA,选择位于15q22.31-q23及18q21.1区域7个微卫星标记,应用聚合酶链式反应(PCR)得到扩增产物片断,测定PCR产物片段大小,得到每个样本的基因型,运用连锁分析软件Linkage5.11的MLINK程序计算每个标记的LOD值,根据两点间LOD值判断连锁关系。结果D15S108、D15S216、D15S534、D18S363、D18S846五个位点的两点LOD值在重组率为0时均小于-2,可以排除连锁关系,而D18S460、D18S467两位点在重组率θ为0.05和0.10时的两点LOD值均大于1,D18S460在θ=0时大于2,提示此家系keloid易感基因与这两个位点存在一定连锁关系。结论此汉族keloid家系的易感基因可能位于染色体18q21.1区域内,初步确定SMAD2和PIAS2基因为可能的易感基因。     

瘢痕疙瘩易感基因的家系连锁分析定位研究

目的:探讨瘢痕疙瘩(keloid)家系中易感基因与15q22.31￣q23及18q21.1区域的连锁关系。方法:1个中国东北地区4代瘢痕疙瘩家系,采集家系中32名成员的外周血标本提取DNA,选择位于15q22.31￣q23及18q21.1区域7个微卫星标记,应用聚合酶链式反应(PCR)得到扩增产物片断,测定PCR产物片段大小,得到每个样本的基因型。运用连锁分析软件LINKAGE的MLINK程序计算每个标记的LOD值,根据两点间LOD值判断连锁关系。结果:D15S108、D15S216、D15S534、D18S363、D18S846五个位点的两点LOD值在重组率为0时均小于-2,可以排除此家系疾病候选基因与上述位点的连锁关系,而D18S460、D18S467两位点在重组率为0.05和0.10时的两点LOD值均大于1,且外显率为90%的条件下,D18S460在θ=0时LOD值大于2,提示此家系瘢痕疙瘩易感基因与这两个位点存在一定的连锁关系。结论:此瘢痕疙瘩家系的易感基因可能位于18q21.1区域内。     

福建省两个汉族瘢痕疙瘩家系与染色体18q21．1的连锁分析

目的：探讨福建省两个汉族瘢痕疙瘩家系是否与18q21．1存在连锁关系。方法：收集来自福建省不同地区的两个汉族瘢痕疙瘩家系,分别命名为A和B家系,从中选出26名具有较高遗传学研究意义的成员作为研究对象,采集他们的外用静脉血样,提取基因组DNA。设定与瘢痕疙瘩形成关系密切的SMAD2、SMAD4、SMAD7及PIAS2基因为导致家系发病的候选基因,选取这些基因所在的染色体18q21．1区域内与其紧邻的微卫星标记D18S1312、D18S1327、D18S547、D18S1291;对这些微卫星位点进行PCR扩增,产物片断基因分型和连锁分析。结果：A家系微卫星标记D18S1291LOD。为0．89,D18S1312LODZMX。为0．82,D18S547LODZMX为0．75,可以排除连锁：在0=0．0～0．10时,D18s1327标记的所有LOD值都小于-2,排除连锁。B家系微卫星标记DI8S1291LODⅢ为0．84,D18S1312LODM为0．78,D18S547LODZMX为0．63,可以排除连锁;在O=0．0～0．10时,D18S1327标记的所有LOD值都小于一2,排除连锁。结论：本研究提示这两个来自福建的汉族瘢痕疙瘩家系的易感基因位点不在染色体18q21．1区域。     

福建省两个汉族瘢痕疙瘩家系易感基因的定位研究

目的：开展汉族瘢痕疙瘩家系易感基因定位研究。方法：收集来自福建省不同地区的两个汉族瘢痕疙瘩家系，分别命名为A和B家系，从中选出26名具有较高遗传学研究意义的成员作为研究对象，采集他们的外周静脉血样，提取基因组DNA；设定Fas基因为导致家系发病的一个候选基因，选取位于10q23．31上Fas基因周围共约10Mbp范围内与细胞凋亡障碍或肿瘤发生有关的所有已知基因相邻的微卫星标记D10S1687、D10S1765、D10S1735和D10S1562共4个，对这些微卫星位点进行PCR扩增，产物片断基因分型和连锁分析。结果：A家系微卫星标记D10S1765LODZMAX为1．86，D10S1735LODZMAX为1．29，支持连锁；D10S1562LODZMAX为0．42，不排除连锁；在O=0．0～0．10时，D10S1687标记的所有LOD值都小于-2，排除连锁。B家系微卫星标记D10S1765LODZMAX为1．63，D10S1735LODM为1．37，支持连锁；D10S1562LODZMAX为0．25，不排除连锁；在0=0．0～0．10时，D10S1687标记的所有LOD值都小于-2，排除连锁。结论：本研究提示这两个来自福建的汉族瘢痕疙瘩家系的易感基因可能位于10q23．31上D10S1765与D10S1735两位点间约1Mbp区域。     

中国汉族一瘢痕疙瘩家系易感基因的定位研究

目的定位中国汉族瘢痕疙瘩家系的易感基因。方法采集1个5代发病的中国汉族瘢痕疙瘩大家系32名成员的外周静脉血样,提取基因组DNA;设定Fas基因为导致该家系发病的一个候选基因,选取位于10q23.31上Fas基因周围共约10Mbp范围内与细胞凋亡障碍或肿瘤发生有关的所有已知基因相邻的微卫星标记D10S1687、D10S1765、D10S1735和D10S1562共4个,对这些微卫星位点进行PCR扩增,产物片断基因分型和连锁分析。结果连锁分析发现微卫星标记D10S1765LODZMAX为1.74,D10S1735LODZMAX为1.51,支持连锁;D10S1562LODZMAX为0.59,不排除连锁;在θ=0.0～0.10时,D10S1687标记的所有LOD值都小于-2,排除连锁。结论我们的研究首次发现了该中国汉族瘢痕疙瘩家系的易感基因可能位于10q23.31上D10S1765与D10S1735两位点间约1Mbp区域的遗传学证据。     

一个中国汉族家族性IgA肾病家系致病基因的排除性定位

目的 对一个中国汉族家族性IgA肾病（FIgAN）家系进行遗传连锁分析,并对目前国内外已知的5个致病位点进行排除性定位,从而初步定位该家系致病基因的染色体位点。 方法 判断FIgAN的遗传方式。采集家系成员外周血提取基因组DNA。在已报道的FIgAN致病区域（2q36、3p23-24、4q26-31、6q22-23、17q12-22）选取微卫星遗传标记（STR）,进行基因组扫描,应用两点间连锁分析方法对基因分型数据进行分析。结果 该FIgAN家系的遗传方式为常染色体显性遗传。对该家系5个已知致病区域内计26个STR的两点间连锁分析结果显示,最大优势对数（LOD）值为0.39（D17S1868）,不支持与上述5个染色体区域的连锁关系。 结论 该家系致病基因所在染色体区域非目前已报道的5个FIgAN致病位点,提示FIgAN存在新的致病区域,并进一步证明了该病的遗传异质性。     

三个汉族瘢痕疙瘩家系调查

目的：开展汉族瘢痕疙瘩家系的遗传学研究。方法：收集无亲缘关系的汉族瘢痕疙瘩家系的临床资料,绘制家系图谱,抽取部分家系成员的外周静脉血样。结果：三个汉族瘢痕疙瘩家系中四代家系1个,三代家系2个;家系成员共62人,发病13人,可疑发病1人,2个未发病肯定携带者,1个未发病可疑携带者;三代发病家系1个,两代发病家系2个;采集家系成员外周静脉血样37份。结论：这三个汉族瘢痕疙瘩家系的遗传模式符合常染色体显性遗传伴外显不完全,家系调查有助于瘢痕疙瘩的进一步遗传学研究。     

Examination of candidate chromosomal regions for type 2 diabetes reveals a susceptibility locus on human chromosome 8p23.1

In a panel of large Caucasian pedigrees, we genotyped markers in eight chromosomal regions previously reported as supporting linkage with type 2 diabetes. We previously reported significant linkage on chromosome 20q (maximum logarithm of odds score [MLS] = 2.79) in this panel. In the present analysis, candidate regions on 1q, 2q, 3q, 5q, 9q, and 10q yielded little evidence for linkage; a region on 2p (MLS = 1.64, P = 0.01 at position 9.0 cM) gave suggestive evidence of linkage; and a region on 8p (MLS = 3.67, P = 2.8 x 10(-5), at position 7.6 cM) gave significant evidence of linkage. Conditional analyses were performed for both 2p and 8p regions and the region reported on 20q. The MLS for 2p increased from 1.64 to 1.79 (empirical P = 0.142) when conditioned for heterogeneity on 20q. The case was similar for 8p, where the MLS increased from 3.67 to 4.51 (empirical P = 0.023) when conditioned on families without evidence of linkage at 20q. In conclusion, our data support a type 2 diabetes susceptibility locus on chromosome 8p that appears to be independent from other susceptibility loci. Although we were able to replicate linkage in our pedigrees on chromosome 2p, we did not find evidence of linkage for regions on 1q, 2q, 3q, 5q, 9q, or 10q.     

Localization of dominantly inherited isolated triphalangeal thumb to chromosomal region 7q36.

Triphalangeal thumb is an autosomal dominantly inherited form of abnormal preaxial skeletal development. In most families, however, the triphalangeal thumb phenotype coexists with a spectrum of limb deformities, including polydactyly and syndactyly. We describe two Iowa kindreds with triphalangeal thumb. In one family, with nine affected members, triphalangeal thumb was the only manifestation of limb deformity. We performed linkage analysis on both pedigrees, demonstrating a maximum LOD score of 6.23 with marker D7S559 on chromosome 7q36. This corresponds to a previous study of a candidate region of 450 kb in which data from several families with preaxial polydactyly were employed. Further analysis of the unique family with isolated triphalangeal thumb in the current study may demonstrate allelic variability of the gene involved in these disorders.     

Linkage of the metabolic syndrome to 1q23-q31 in Hispanic families: the Insulin Resistance Atherosclerosis Study Family Study

The metabolic syndrome is characterized by central obesity, dyslipidemia, elevated blood pressure, and hyperglycemia. The Insulin Resistance Atherosclerosis Study (IRAS) Family Study recruited extended pedigrees of Hispanic descent from San Antonio, TX (SA) and San Luis Valley, CO (SLV). Thirty-five of these pedigrees (27 SA and 8 SLV) had at least 2 individuals with metabolic syndrome (216 affected individuals and 563 affected relative pairs). The prevalence of metabolic syndrome and component criteria in subjects from these pedigrees were 35% metabolic syndrome, 43% increased waist circumference, 31% hypertriglyceridemia, 69% low HDL cholesterol, 31% increased blood pressure, and 25% either increased fasting glucose or presence of diabetes. Nonparametric linkage analysis provided evidence for linkage of metabolic syndrome to 1q23-q31 (D1S518; logarithm of odds [LOD] 1.6) with significant site heterogeneity (SA LOD 2.6 and SLV LOD 0.0), and removing all individuals with diabetes reduced, but did not eliminate, the evidence for linkage to this region (LOD 1.2). This heterogeneity may partially be explained by phenotypic differences. Members in the SA pedigrees were older, had greater central obesity, had higher prevalence of the metabolic syndrome, and were from a more urban environment than members of the SLV pedigrees. These results contribute to the growing evidence that chromosome 1q harbors at least one locus related to the metabolic precursors of diabetes.     

Genome-wide scan for prostate cancer susceptibility genes using families from the University of Michigan prostate cancer genetics project finds evidence for linkage on chromosome 17 near BRCA1

BACKGROUND: Previous linkage studies have suggested prostate cancer susceptibility genes located on chromosomes 1, 20, and X. Several putative prostate cancer candidate genes have also been identified including RNASEL, MSR1, and ELAC2. Presently, these linkage regions and candidate genes appear to explain only a small proportion of hereditary prostate cancer cases suggesting the need for additional whole genome analyses. METHODS: A genome-wide mode-of-inheritance-free linkage scan, using 405 genetic markers, was conducted on 175 pedigrees, the majority containing three or more affected individuals diagnosed with prostate cancer. Stratified linkage analyses were performed based on previously established criteria. RESULTS: Results based on the entire set of 175 pedigrees showed strong suggestive evidence for linkage on chromosome 17q (LOD = 2.36), with strongest evidence coming from the subset of pedigrees with four or more affected individuals (LOD = 3.27). Race specific analyses revealed strong suggestive evidence for linkage in our African-American pedigrees on chromosome 22q (LOD = 2.35). CONCLUSIONS: Genome-wide analysis of a large set of prostate cancer families indicates new areas of the genome that may harbor prostate cancer susceptibility genes. Specifically, our linkage results suggest that there is a prostate cancer susceptibility gene on chromosome 17 that is independent of ELAC2. Further research including combined analyses of independent genome-wide scan data may clarify the most important regions for future investigation.     

Genome-wide search for type 2 diabetes/impaired glucose homeostasis susceptibility genes in the Chinese: significant linkage to chromosome 6q21-q23 and chromosome 1q21-q24

This genome-wide search for susceptibility genes to type 2 diabetes/impaired glucose homeostasis (IGH) was performed on a relatively homogeneous Chinese sample with a total number of 257 pedigrees and 385 affected sibpairs. Two regions showed significant linkage to type 2 diabetes/IGH in the Chinese. The region showing linkage to type 2 diabetes/IGH from the entire sample group analysis was located on chromosome 6q21-q23 (128.93 cM, 1-LOD [logarithm of odds] support interval between 124 and 142 cM, according to the Marshfield genetic map), with a maximum likelihood score of 6.23, a nonparametric linkage (all) score of 4.48, and empirical P value <0.001. With a subanalysis based on 101 affected sibpairs with age at diagnosis of type 2 diabetes/IGH <40 years, we detected significant evidence for linkage to chromosome 1q21-q24 (192.1 cM, 1-LOD support interval between 182 and 197 cM), with a maximum likelihood score of 8.91, a nonparametric linkage (all) score of 5.70, and empirical P value <0.001. No interaction was observed between these two regions. Our independent replication of the region on chromosome 1q that has been shown to be linked significantly to type 2 diabetes/IGH in Chinese supports the notion that gene(s) in this region may be universally important in the development of human type 2 diabetes.