CONSORTIUM-BACED LINKAGE ANALYSIS AND IDENTIFICATION OF GENES FOR SINGEL-GENE DISEASES

基于联盟的连锁分析和单基因疾病基因鉴定

• 批准号: 13854024
• 负责人: NIIKAWA Norio
• 金额: $ 72.97万
• 依托单位: NAGASAKI UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (S)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13854024/
• 关键词: linkage analysis; single-gene disorders; gene mapping; disease genes; familial cases of genetic diseases; 家族性心房中核欠損症; 多汗症; 下顎前突症; 無嗅覚症; 心房中隔欠損症; ハプロタイプ解析; 家族性側索硬化症; 無臭覚症; 緊張性四肢麻痺; 疾患遺伝子座; 単一遺伝子疾患; マイクロサテライトマーカー; 変異解析; 疾病遺伝子; WFS1遺伝子; 遺

This research aimed to collect many cases of single-gene disorders of unknown cause by a consortium from all of Japan and to map the disease loci and identify genes for the diseases. During a 5-year-period of the research, we performed linkage analysis of 14 such disorders (including genetic traits) and identified novel gene mutations in 8 disorders. The followings are the details of the diseases studied : (1)Retinitis pigmentosa : by linkage analysis, we assigned disease loci of 3 Japanese and 2 Thai families, and identified RPGR and NDP mutations, respectively ; (2)Engelmann disease : as a linkage analysis found two Engelmann disease families in which disease loci did not correspond the TGFB1 locus, we proposed the disease in the families is a new clinical entity, Engelmann disease type 2 ; (3)Familial hearing impairment : linkage analysis of a large family mapped the locus and identified a novel mutation ; (4)Van der Woude syndrome : the diseases of two families were both mapped to … More 1q32-q41, and mutations in IRF6 were identified in each family ; (5)Anosmia : we found two large Iranian families, and mapped the disease locus within a region between D18S452 and D18S475 ; (6)Familial ASD : linkage analysis of one large family led to the disease gene localization to 8p23-p22, and mutation analysis identified a one-base deletion in GATA4 ; (7)Spastic paraplegia : linkage analysis of one big family mapped the disease to 2p23 and mutation study identified a large intragenic deltion in SPG4 ; (8)Palmoplantar hyperhydrosis : linkage analysis of 11 families assigned the disease of three families to 14q11.2, but locus heterogeneity was evident ; (9)Epidermolysis bullosa : linkage and mutation analysis of one family identified a novel mutation in COL17A1 ; (10)Human earwax trait : linkage analysis mapped the earwax locus to 16p11.2-q12.1, and subsequent association study using SNPs identified a functional SNP in ABCC11 as the earwax determinant ; (11)Familial thrombocytopenia : linkage analysis mapped the disease between D17S950 and D17S1607 ; (12)Familial amyotropic lateral sclerosis : linkage analysis of one family mapped the disease to either 1p or 17q ; (13)and(14)Familial prognathism and Familial blepharoptosis : In neither diseases, disease loci were assigned, because of locus heterogeneity was evident. Less

本研究的目的是通过一个财团从日本全国收集许多原因不明的单基因疾病病例，并绘制疾病位点图和识别疾病基因。在为期5年的研究中，我们对14种此类疾病（包括遗传性状）进行了连锁分析，并在8种疾病中发现了新的基因突变。以下是所研究疾病的详细信息：（1）视网膜色素变性：通过连锁分析，我们分配了3个日本和2个泰国家庭的疾病位点，并分别鉴定了RPGR和NDP突变;（2）Engelmann病：由于连锁分析发现两个Engelmann病家族的疾病基因座不对应于TGFB 1基因座，我们提出该家族中的疾病是一种新的临床实体，Engelmann病2型;（3）家族性听力损害：对一个大家族进行连锁分析，定位了基因座，并发现了一个新的突变;（4）货车der Woude综合征：两个家族的疾病都被定位， ...更多信息 1 q32-q41，每个家系均发现IRF 6基因突变;（5）嗅觉缺失：发现两个伊朗家系，并将致病基因定位在D18 S452和D18 S475之间的区域内;（6）家族性ASD：一个家系的连锁分析将致病基因定位在8 p23-p22，突变分析发现GATA 4基因有一个碱基缺失;（7）痉挛性截瘫：一个大家系的连锁分析将该病定位于2 p23，突变研究发现SPG 4有一个大的基因内缺失;（8）掌跖多汗症：11个家系的连锁分析将3个家系的疾病定位于14q11.2，但位点异质性明显;（9）大疱性表皮病：一个家族的连锁和突变分析鉴定了COL 17 A1中的新突变;（10）人类耳垢性状：连锁分析将耳垢位点定位在16p11.2-q12.1，随后使用SNP的关联研究鉴定了ABCC 11中的功能性SNP作为耳垢决定因子;（11）家族性血小板减少症：连锁分析将疾病定位在D17 S950和D17 S1607之间;（12）家族性肌萎缩侧索硬化症：一个家族的连锁分析将该疾病定位于1 p或17 q;（13）和（14）家族性下颌骨肥大和家族性眼睑下垂：在这两种疾病中，由于基因座异质性很明显，疾病基因座都没有被分配。少

项目成果

A Thai mother and son with distal symphalangism, hypoplastic carpal bones, microdontia, dental pulp stones, and narrowing of the zygomatic arch : a new distal symphalangism syndrome?

一对泰国母子患有远端共指症、腕骨发育不全、小牙、牙髓结石和颧弓狭窄：一种新的远端共指症综合征？

• 发表时间: 2002
• 期刊: Am J Med Genet 109(1)
• 作者: Kantaputra PN;Kinoshita A;Limwonges C;Praditsup O;Niikawa N
• 通讯作者: Niikawa N

Matsuzawa N 他: "A T25G mutation in the IRF6 gene in a Japanese family with Van der Woude syndrome"Oral Surg, Oral Med, Oral Pathol, Oral Radiol, Endodont. (In press).

Matsuzawa N 等人：“患有 Van der Woude 综合征的日本家庭中 IRF6 基因的 T25G 突变”Oral Surg、Oral Med、Oral Pathol、Oral Radiol、Endodont（正在出版）。

Kinoshita A 他: "TGFB1 mutations in four new families with Camurati-Engelmann disease : Confirmation of independently arising LAP-domain-specific mutations"Am J Med Genet. (In press).

Kinoshita A 等人：“Camurati-Engelmann 病四个新家族中的 TGFB1 突变：独立产生的 LAP 域特异性突变的确认”Am J Med Genet（正在出版）。

Ghadami M 他: "Familial isolated congenital anosmia with morphologically normal olfactory bulb in two unrelated Iranian families : A new clinical entity?"Am J Med Genet. (In press).

Ghadami M 等人：“两个无关的伊朗家庭中具有形态正常嗅球的家族性孤立性先天性嗅觉缺失：一个新的临床实体？”Am J Med Genet（正在出版）。

Peeters H 他: "PA26 is a candidate gene for heterotaxia in humans : Identification of a novel, PA26-related gene family in human and mouse"Hum Genet. 112. 573-580 (2003)

Peeters H 等人：“PA26 是人类异位症的候选基因：人类和小鼠中新型 PA26 相关基因家族的鉴定”Hum Genet. 112. 573-580 (2003)