DNA sequence and analysis of human chromosome 18

Nature, 2004

Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb.

Nature, 2003

Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb.

Genomics, 1996

genes mapped by linkage, which, in turn, allowed many A panel of somatic cell hybrids carrying a defined of the markers already assigned physical locations usset of rearrangements involving chromosome 13 has ing the same hybrids Kooy et been used to assign 35 novel gene transcripts regional., 1994) to be incorporated into a more detailed physially. The positions of the chromosome 13 breakpoints cal map. The improved physical and genetic maps of in each somatic cell hybrid have previously been dechromosome 13 have also allowed the isolation of YACs fined relative to the Gé né thon genetic linkage map. As spanning many megabases, especially around genes of a result, the position of each gene transcript has been medical importance . Thus, determined relative to both the physical and the gethe search for the Wilson disease gene generated a netic linkage maps. Analysis of the distribution of large contig in 13q21 which we have these gene transcripts indicates a slight overrepresenextended through the BCLL and RB1 loci and even tation toward locations on the distal long arm of chromore proximal . The BRCA2 mosome 13, with no localizations noted in the 13q22locus is also now covered with YACs (Kelsell et al., q31 region. Seven of these novel gene transcripts and in preparation), and we have prepared extensive YAC the gene encoding small ribonucleoprotein U6 have contigs in the 13q12 region, which is the site of chromobeen mapped to YACs known to contain Gé né thon misome translocation breakpoints associated with ganglicrosatellite markers, thereby providing further sublooneuroblastoma (Michalski and Cowell, 1993) and a calization relative to the genetic map. The positioning form of myeloproliferative disease (Kempski et al., of these gene transcripts within the genetic and physical maps provides candidate genes for disease loci that 1995). are being mapped to the same intervals on the chromo-

Nature, 2006

After the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evo...

Nature, 2003

Chromosome 19 has the highest gene density of all human chromosomes, more than double the genome-wide average. The large clustered gene families, corresponding high G1C content, CpG islands and density of repetitive DNA indicate a chromosome rich in biological and evolutionary significance. Here we describe 55.8 million base pairs of highly accurate finished sequence representing 99.9% of the euchromatin portion of the chromosome. Manual curation of gene loci reveals 1,461 protein-coding genes and 321 pseudogenes. Among these are genes directly implicated in mendelian disorders, including familial hypercholesterolaemia and insulin-resistant diabetes. Nearly one-quarter of these genes belong to tandemly arranged families, encompassing more than 25% of the chromosome. Comparative analyses show a fascinating picture of conservation and divergence, revealing large blocks of gene orthology with rodents, scattered regions with more recent gene family expansions and deletions, and segments of coding and non-coding conservation with the distant fish species Takifugu.