Alternative titles; symbols
HGNC Approved Gene Symbol: HYDIN2
Cytogenetic location: 1q21.1 Genomic coordinates (GRCh38): 1:146,486,332-146,822,034 (from NCBI)
By sequencing clones obtained from a size-fractionated fetal brain cDNA library, Nagase et al. (2001) cloned HYDIN2, which they designated KIAA1864. RT-PCR ELISA detected moderate HYDIN2 expression in adult and fetal brain, spinal cord, and all specific brain regions examined. Lower expression was detected in lung, kidney, testis, and ovary, and little to no expression was detected in other tissues examined.
By genomic sequence analysis, Doggett et al. (2006) identified a duplicated copy of HYDIN (610812), HYDIN2, on chromosome 1. Database and sequence analyses revealed HYDIN transcripts that had been isolated from lung, testis, NT2 neuronal precursor cells, and Jurkat leukemic T cells, whereas HYDIN2 transcripts had been isolated from brain and NT2 cells only. Both genes appeared to be expressed as alternatively spliced transcripts.
Doggett et al. (2006) determined that the HYDIN2 gene contains 79 exons and spans approximately 360 kb. It lacks the first 5 exons and last 2 exons of the HYDIN gene.
Using radiation hybrid analysis, Nagase et al. (2001) mapped the HYDIN2 gene to both chromosome 1 and chromosome 16. By genomic sequence analysis, Doggett et al. (2006) determined that the HYDIN2 gene maps to chromosome 1q21.1 and is a duplicated copy of the HYDIN gene on chromosome 16q22.2.
Using PCR and FISH, Doggett et al. (2006) confirmed that duplication of the HYDIN gene is specific to humans. A large and diverse sample of humans contained both HYDIN and HYDIN2, and there was no evidence for polymorphic presence of HYDIN2.
Brunetti-Pierri et al. (2008) found that patients with 1q21 deletion phenotype (612474) had microcephaly, whereas patients with microduplication of this region (612475) had macrocephaly. They postulated that dosage sensitivity of the HYDIN2 gene was responsible for the variation in head circumference.
By analyzing short-read mapping depth for 159 human genomes, Sudmant et al. (2010) demonstrated accurate estimation of absolute copy number for duplications as small as 1.9 kb pairs, ranging from 0 to 48 copies. Sudmant et al. (2010) identified 4.1 million 'singly unique nucleotide' positions informative in distinguishing specific copies and used them to genotype the copy and content of specific paralogs within highly duplicated gene families. These data identified human-specific expansions in genes associated with brain development, such as GPRIN2 (611240) and SRGAP2 (606524), which have been implicated in neurite outgrowth and branching. Also included were the brain-specific HYDIN2 gene, associated with micro- and macrocephaly; DRD5 (126453), a dopamine D5 receptor; and the GTF2I (601679) transcription factors, whose deletion has been associated with visual-spatial and sociability deficits among Williams-Beuren syndrome (194050) patients, among others. The data of Sudmant et al. (2010) also revealed extensive population genetic diversity, especially among the genes NPEPPS (606793), UGT2B17 (601903), and NBPF1 (610501), as well as LILRA3 (604818), which is the most highly stratified gene by copy number in the human genome. In addition, Sudmant et al. (2010) detected signatures consistent with gene conversion in the human species.
Brunetti-Pierri, N., Berg, J. S., Scaglia, F., Belmont, J., Bacino, C. A., Sahoo, T., Lalani, S. R., Graham, B., Lee, B., Shinawi, M., Shen, J., Kang, S.-H. L., and 28 others. Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities. Nature Genet. 40: 1466-1471, 2008. [PubMed: 19029900] [Full Text: https://doi.org/10.1038/ng.279]
Doggett, N. A., Xie, G., Meincke, L. J., Sutherland, R. D., Mundt, M. O., Berbari, N. S., Davy, B. E., Robinson, M. L., Rudd, M. K., Weber, J. L., Stallings, R. L., Han, C. A 360-kb interchromosomal duplication of the human HYDIN locus. Genomics 88: 762-771, 2006. [PubMed: 16938426] [Full Text: https://doi.org/10.1016/j.ygeno.2006.07.012]
Nagase, T., Nakayama, M., Nakajima, D., Kikuno, R., Ohara, O. Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 8: 85-95, 2001. [PubMed: 11347906] [Full Text: https://doi.org/10.1093/dnares/8.2.85]
Sudmant, P. H., Kitzman, J. O., Antonacci, F., Alkan, C., Malig, M., Tsalenko, A., Sampas, N., Bruhn, L., Shendure, J., 1000 Genomes Project, Eichler, E. E. Diversity of human copy number variation and multicopy genes. Science 330: 641-646, 2010. [PubMed: 21030649] [Full Text: https://doi.org/10.1126/science.1197005]