TY - JOUR
T1 - Nucleotide sequencing analysis of the 146-kilobase segment around the IkBL and MICA genes at the centromeric end of the HLA class I region
AU - Shiina, Takashi
AU - Tamiya, Gen
AU - Oka, Akira
AU - Yamagata, Tetsushi
AU - Yamagata, Naomi
AU - Kikkawa, Eri
AU - Goto, Kaori
AU - Mizuki, Nobuhisa
AU - Watanabe, Koji
AU - Fukuzumi, Yasuhito
AU - Taguchi, Susumu
AU - Sugawara, Chiyo
AU - Ono, Ayako
AU - Chen, Lei
AU - Yamazaki, Masaaki
AU - Tashiro, Hiroyuki
AU - Ando, Asako
AU - Ikemura, Toshimichi
AU - Kimura, Minoru
AU - Inoko, Hidetoshi
N1 - Funding Information:
We thank Dr. Stephan Beck for critically reading the manuscript and for helpful discussion. This work was supported by the Japan Information Center of Science and Technology, an arm of the Science and Technology Agency.
PY - 1998/2/1
Y1 - 1998/2/1
N2 - To elucidate the complete gene structure and to identify new genes involved in the development of HLA class I antigen-associated diseases in the class I region of the human major histocompatibility complex on chromosome 6, a YAC clone (745D12) covering the 146-kb segment around the IkBL and MICA loci was isolated from a YAC library constructed from the B-cell line, BOLETH. A physical map of this region was constructed by isolation of overlapping cosmid clones derived from 745D12. Of these, five contiguous cosmids were chosen for DNA sequencing by the shotgun strategy to give a single contig of 146,601 bp from 2.8 kb telomeric of the IkBL gene to exon 6 of MICA. This region was confirmed to contain five known genes, IkBL, BAT1, MICB, P5-1, and HLA.X (class I fragment), from centromere to telomere, and their exon-intron organizations were determined. The 3.8-1 homologue gene (3.8-1-hom) showing 99.7% identity with the 3.8-1 cDNA clone, which was originally isolated using the 3.8-kb EcoRI fragment between the HLA-54/H and the HLA-G genes, was detected between MICA and MICB and was suggested to represent the cognate 3.8-1 genomic sequence from which the cDNA clone was derived. No evidence for the presence of expressed new genes could be obtained in this region by homology and EST searches or coding and exon prediction analyses. One TA microsatellite repeat spanning 2545 bases with as many as 913 repetitions was found on the centromeric side of the MICA gene and was indicated to be a potential hot spot for genetic recombination. The two segments of approximately 35 kb upstream of the MICA and MICB genes showed high sequence homology (about 85%) to each other, suggesting that segmental genome duplication including the MICA and MICB genes must have occurred during the evolution of the human MHC.
AB - To elucidate the complete gene structure and to identify new genes involved in the development of HLA class I antigen-associated diseases in the class I region of the human major histocompatibility complex on chromosome 6, a YAC clone (745D12) covering the 146-kb segment around the IkBL and MICA loci was isolated from a YAC library constructed from the B-cell line, BOLETH. A physical map of this region was constructed by isolation of overlapping cosmid clones derived from 745D12. Of these, five contiguous cosmids were chosen for DNA sequencing by the shotgun strategy to give a single contig of 146,601 bp from 2.8 kb telomeric of the IkBL gene to exon 6 of MICA. This region was confirmed to contain five known genes, IkBL, BAT1, MICB, P5-1, and HLA.X (class I fragment), from centromere to telomere, and their exon-intron organizations were determined. The 3.8-1 homologue gene (3.8-1-hom) showing 99.7% identity with the 3.8-1 cDNA clone, which was originally isolated using the 3.8-kb EcoRI fragment between the HLA-54/H and the HLA-G genes, was detected between MICA and MICB and was suggested to represent the cognate 3.8-1 genomic sequence from which the cDNA clone was derived. No evidence for the presence of expressed new genes could be obtained in this region by homology and EST searches or coding and exon prediction analyses. One TA microsatellite repeat spanning 2545 bases with as many as 913 repetitions was found on the centromeric side of the MICA gene and was indicated to be a potential hot spot for genetic recombination. The two segments of approximately 35 kb upstream of the MICA and MICB genes showed high sequence homology (about 85%) to each other, suggesting that segmental genome duplication including the MICA and MICB genes must have occurred during the evolution of the human MHC.
UR - http://www.scopus.com/inward/record.url?scp=0032006134&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032006134&partnerID=8YFLogxK
U2 - 10.1006/geno.1997.5114
DO - 10.1006/geno.1997.5114
M3 - Article
C2 - 9480751
AN - SCOPUS:0032006134
VL - 47
SP - 372
EP - 382
JO - Genomics
JF - Genomics
SN - 0888-7543
IS - 3
ER -