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

Abstract

We have sequenced 1949 kb from the terminal Giemsa light band of human chromosome 16p, enabling us to fully annotate the region extending from the telomeric repeats to the previously published tuberous sclerosis disease 2 (TSC2) and polycystic kidney disease 1 (PKD1) genes. This region can be subdivided into two GC-rich, Alu-rich domains and one GC-rich, Alu-poor domain. The entire region is extremely gene rich, containing 100 confirmed genes and 20 predicted genes. Many of the genes encode widely expressed proteins orchestrating basic cellular processes (e.g. DNA recombination, repair, transcription, 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 are known disease genes for alpha thalassaemia, adult polycystic kidney disease and tuberous sclerosis. There is also linkage evidence for bipolar affective 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 human telomeric region.

Common variants in the UBC9 gene encoding the SUMO‐conjugating enzyme are associated with breast tumor grade

“…Furthermore, one previous study using an in silico approach to predict putative genes on the short arm of chromosome 16 suggested an open reading frame encompassing rs7187167. 29 Thus, we cannot exclude the possibility that this polymorphism may influence the function of a yet unidentified protein.…”

-Thalassemia, Mental Retardation, and Myelodysplastic Syndrome

“…However, although deleted in case WG ( Fig. 1) (Gibson et al 2008), the deletion in TN does not extend to SOX8 (Daniels et al 2001). Furthermore, a recently described Brazilian patient with a deletion that removes both the a globin locus and SOX8 was not associated with MRor any dysmorphism (Bezerra et al 2008).…”

“…The region lying between 900-1700 kb from the 16p telomere, deleted in all patients with the characteristic features of ATR-16 syndrome, contains 14 genes and gene families of known function (Daniels et al 2001) that have been implicated in awide range of disorders with few or no features in common with ATR-16. One of these (SOX8) was considered a strong candidate because it is involved in the regulation of embryonic development and is strongly expressed in the brain (Pfeifer et al 2000).…”

The Molecular Basis of -Thalassemia

“…This series of up-regulatory events taking place in erythroid cells is only a part of the complete story of a-globin regulation. Although the a-globin genes are expressed in a strictly tissuespecific manner, they are contained in a large chromosomal region, which is broadly transcriptionally active and bears the hallmarks of constitutively active chromatin (Flint et al 1997;Daniels et al 2001). Therefore, it was predicted that within such a region, mechanisms should exist to maintain the a-globin genes in a silent state in nonerythroid cells.…”