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

两个大的人类基因组序列contigs已分析与设置

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.