The DNA sequence and biology of human chromosome 19

Abstract

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.

DNA sequence and analysis of human chromosome 18

“…There is evidence of extensive alternative splicing, with gene loci having an average of 3.1 distinct transcripts and 71% having at least two transcripts. This rate of alternative splicing is comparable to recent reports 5,6 . The longest gene on chromosome 18 is DCC (deleted in colorectal carcinoma), spanning 1,190,632 bp.…”

Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution

“…Conserved non-coding regions are clustered and far from genes Several recent human-rodent comparisons [146][147][148] within limited regions of the genome have observed that conserved non-coding segments tend to lie relatively far from genes. To investigate whether this holds true across the genome in human-chicken comparisons, we partitioned the human genome into non-overlapping intervals, and in each interval (after excluding repetitive nucleotides) computed the fraction that falls in a coding exon annotated by RefSeq or Ensembl (the 'coding fraction') and the fraction that aligns with chicken but does not intersect coding exons (the 'conserved noncoding fraction' or CNF), taking care to keep the two quantities logically independent (see Methods).…”

Epigenetic regulation mechanisms of microRNA expression

“…A feasible explanation for this may lie in the fact that chromosome 19 is rich in biological and evolutionary significance with the highest gene density of all human chromosomes. In addition, the GC content of the chromosome is unusually high (48% vs. 41% of the median whole human genome) with two-thirds of genes having at least one CpG island (30). In contrast, chromosome Y has evolved by a gene loss leading to a paucity of genes, which correlates with the paucity of CpG islands (31).…”