KALLMANN'S SYNDROME GENE (XP22) AND NEW GENES IN THE HLA CLASS III REGION (6P21)

卡尔曼综合征基因 (XP22) 和 HLA III 类区域的新基因 (6P21)

• 批准号: 3845102
• 负责人: J M CLAVERIE
• 金额: --
• 依托单位: NATIONAL LIBRARY OF MEDICINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3845102
• 关键词: Kallmann's syndrome; computer assisted sequence analysis; computer program /software; fibronectins; genome; histocompatibility gene; human genetic material tag; information systems; male; molecular genetics; nucleic acid repetitive sequence; protease inhibitor; protein sequence; sex chromosomes; structural genes; transcription factor

Two large human genomic sequence contigs have been analyzed with the set of programs (BLAST, XNU, Xblast, EXON, etc) and databanks (NRDB, Geninfo) uniquely available at NCBI. Those studies have lead to the identification of the gene for Kallmann's syndrome (ADML-X, Xp22.3) and of a putative new transcription factor in the HLA class III region (6p21.3). 1) Identification of the Kallmann's syndrome gene. The X-linked Kallmann's syndrome (affecting 1/10000 male) is defined by simultaneous defects in the migration of GN-RH neurones and in the fasciculation of the olfactory neurones during the early development of the brain. Molecular genetics analysis led to the sequencing (Institut Pasteur, Genethon) of a 67kb contig in which two exons totalling lesss than 450 nucleotides where identified by a combination of computer analysis techniques. The study of the protein sequence encoded by a full lenght cDNA revealed an original assembly of fibronectin and anti-protease domains, consistent with its role as a neurone targeting molecule. 2) Analysis of a 90kb contig in the HLA class 3 region. The same combination of computer technique was applied to the analysis of a 90 kb sequence contig (CEPH/Genethon). This region revealed an unusually dense clustering of Alu , the genomic structure of the Bat2 gene (25 exons) and a putative new member of the NFkB family of transcription factors.

两个大的人类基因组序列重叠群已被分析与设置 程序（BLAST、XNU、Xblast、EXON等）和数据库（NRDB、Geninfo） 在NCBI唯一可用。这些研究导致了 Kallmann综合征的基因（ADML-X，Xp22.3）和一个假定的新的 在HLA III类区域（6p21.3）中的转录因子。 1)卡尔曼综合征基因的鉴定x连锁 卡尔曼综合征（1/10000男性）定义为同时 GN-RH神经元迁移缺陷和 嗅觉神经元在大脑早期发育过程中的作用。 分子遗传学分析导致测序（巴斯德研究所， Genethon）的一个67 kb重叠群，其中两个外显子总数小于450 其中通过计算机分析和生物信息学分析的组合来鉴定核苷酸 技术.全长编码蛋白质序列的研究 cDNA揭示了纤连蛋白和抗蛋白酶的原始组装 结构域，与其作为神经元靶向分子的作用一致。 2)HLA 3类区域中90 kb重叠群的分析。相同的 结合计算机技术，对一个90 kb 序列重叠群（CEPH/Genethon）。这一区域显示出异常密集的 Alu的聚类、Bat 2基因的基因组结构（25个外显子）和 NF κ B转录因子家族的一个新成员。