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GNASA locus on chromosome 20q13.3 that has a highly complex imprinted expression pattern, giving rise to maternally, paternally and biallelically expressed transcripts derived from four alternative promoters and 5' exons. Some transcripts have a differentially methylated region (DMR) at their 5' exons. This DMR is commonly found in imprinted genes and correlates with transcript expression; one transcript produced from this locus and the antisense transcript are paternally expressed, noncoding RNAs, which may regulate regional imprinting. Alternative splicing of downstream exons results in different forms of the stimulatory G-protein alpha subunit, a key component of the classical signal-transduction pathway linking receptor-ligand interactions to adenylyl cyclase activation and various cellular responses.
GNAS mutations have been linked to pseudohypoparathyroidism types 1a and 1b, Albright hereditary osteodystrophy, pseudopseudohypoparathyroidism, McCune-Albright syndrome, progressive osseus heteroplasia, polyostotic fibrous dysplasia of bone and pituitary tumours.
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Gerontological Society of America.
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