Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16

We have sequenced 1949 kb from the terminal Giemsa light band of human chro mosome 16p, enabling us to fully annotate the region extending from the tel omeric repeats to the previously published tuberous sclerosis disease 2 (TS C2) and polycystic kidney disease 1 (PKD1) genes, This region can be subdiv ided into two GC-rich, Alu-rich domains and one CC-rich, Alu-poor domain, T he entire region is extremely gene rich, containing 100 confirmed genes and 20 predicted genes. Many of the genes encode widely expressed proteins orc hestrating basic cellular processes (e.g. DNA recombination, repair, transc ription, RNA processing, signal transduction, intracellular signalling and mRNA translation). Others, such as the alpha globin genes (HBA1 and HBA2), PDIP and BAIAP3, are specialized tissue-restricted genes. Some of the genes have been previously implicated in the pathophysiology of important human genetic diseases (e.g. asthma, cataracts and the ATR-16 syndrome). Others a re known disease genes for alpha thalassaemia, adult polycystic kidney dise ase and tuberous sclerosis, There is also linkage evidence for bipolar affe ctive disorder, epilepsy and autism in this region. Sixty-three chromosomal deletions reported here and elsewhere allow us to interpret the results of removing progressively larger numbers of genes from this well defined huma n telomeric region.