Genome annotation of a 1.5 Mb region of human chromosome 6q23 encompassing a quantitative trait locus for fetal hemoglobin expression in adults

Autor: Barnaby Clark, Jean Bergounioux, James Close, Ageliki Gerovassili, Laurence Game, Swee Lay Thein
Rok vydání: 2004
Předmět:
Adult
Genetic Markers
lcsh:QH426-470
Hereditary persistence of fetal hemoglobin
Positional cloning
Genes
myb
lcsh:Biotechnology
Pseudogene
Molecular Sequence Data
Quantitative Trait Loci
Nerve Tissue Proteins
Quantitative trait locus
Biology
Peptide Elongation Factor 1
lcsh:TP248.13-248.65
Fetal hemoglobin
Genetics
medicine
Humans
Gene
Fetal Hemoglobin
Adaptor Proteins
Signal Transducing
Expressed Sequence Tags
Expressed sequence tag
Cyclic Nucleotide Phosphodiesterases
Type 7
Genome
Human
Gene Expression Profiling
Alternative splicing
Chromosome Mapping
Computational Biology
Genomics
medicine.disease
Adaptor Proteins
Vesicular Transport
lcsh:Genetics
Gene Expression Regulation
3'
5'-Cyclic-AMP Phosphodiesterases
Organ Specificity
Chromosomes
Human
Pair 6
Pseudogenes
Research Article
Biotechnology
Zdroj: BMC Genomics, Vol 5, Iss 1, p 33 (2004)
BMC Genomics
ISSN: 1471-2164
DOI: 10.1186/1471-2164-5-33
Popis: Background Heterocellular hereditary persistence of fetal hemoglobin (HPFH) is a common multifactorial trait characterized by a modest increase of fetal hemoglobin levels in adults. We previously localized a Quantitative Trait Locus for HPFH in an extensive Asian-Indian kindred to chromosome 6q23. As part of the strategy of positional cloning and a means towards identification of the specific genetic alteration in this family, a thorough annotation of the candidate interval based on a strategy of in silico / wet biology approach with comparative genomics was conducted. Results The ~1.5 Mb candidate region was shown to contain five protein-coding genes. We discovered a very large uncharacterized gene containing WD40 and SH3 domains (AHI1), and extended the annotation of four previously characterized genes (MYB, ALDH8A1, HBS1L and PDE7B). We also identified several genes that do not appear to be protein coding, and generated 17 kb of novel transcript sequence data from re-sequencing 97 EST clones. Conclusion Detailed and thorough annotation of this 1.5 Mb interval in 6q confirms a high level of aberrant transcripts in testicular tissue. The candidate interval was shown to exhibit an extraordinary level of alternate splicing – 19 transcripts were identified for the 5 protein coding genes, but it appears that a significant portion (14/19) of these alternate transcripts did not have an open reading frame, hence their functional role is questionable. These transcripts may result from aberrant rather than regulated splicing.
Databáze: OpenAIRE
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