The DNA sequence and biological annotation of human chromosome 1

Abstract

The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.

Small proline-rich proteins (SPRR) function as SH3 domain ligands, increase resistance to injury and are associated with epithelial–mesenchymal transition (EMT) in cholangiocytes

“…This may explain why the gene locus is so rapidly diverging (9) and a "hotspot" for non-synonymous substitutions (8). Stable expression of SPRR2A in SG231 cells results in changes of cell shape and emergence of mesenchymal characteristics.…”

“…The highest ratio of non-synonymous to synonymous nucleotide substitution rates on human chromosome 1 occurs between SPRR2A and SPRR2F (8) and the EDC is the most rapidly diverging gene cluster comparing human and chimpanzee genomes (9). SPRR diversity lies primarily within the regulatory regions of the SPRR2 gene family (6), which is thought to enable SPRR2 proteins to precisely modify barriers in response to diverse environmental insults (6).…”

A region of 35 kb containing the trace amine associate receptor 6 (TAAR6) gene is associated with schizophrenia in the Irish study of high-density schizophrenia families

“…A similar shift in allele and haplotype frequency has been reported for other genes, where the ancestral haplotype has been supplanted by evolutionarily more recent haplotypes. 55,56 Finally, the issue of multiple testing must also be considered. In our association analyses, multiple testing results from the assessment of multiple markers and multiple haplotypes in conjunction with multiple diagnostic categories.…”

Lelp-1, Its Role in Atopic Dermatitis and Asthma: Poland and Portugal

“…The chromosome 1q21 region [38] has been associated with skin pathology like AD, ichthyosis vulgaris and psoriasis, in a region of about 2.05Mb (mega basis) in Epidermal Differentiation Complex (EDC).…”