Pseudogene

About: Pseudogene is a research topic. Over the lifetime, 5528 publications have been published within this topic receiving 336634 citations. The topic is also known as: Ψ & pseudogenes.

Genetic basis of endocrine disease. 6. Molecular basis of familial human growth hormone deficiency

Abstract: T HE GENE encoding GH-N (GHl) and those genes encoding chorionic somatomammotropin (CSH1,2) hormones reside in a 50,000 base-pair (50 kb) gene cluster on human chromosome 17 (Fig. 1) (1). The GH2 gene also resides in this cluster and encodes a protein (GH-V) that is expressed in the placenta rather than in the pituitary and differs from the primary sequence of GH-N by 13 amino acids. The CSH1,2 genes encode proteins of identical sequences, whereas the CSH pseudogene (CSHPl) encodes a protein differing by 13 amino acids and contains a mutation that should alter its pattern of messenger RNA (mRNA) splicing and thus the primary sequence of the resulting protein (1, 2). The extensive homology (92-98%) between the immediate flanking, intervening, and coding sequences of these 5 genes suggests that this multigene family arose through a series of gene duplication events (1, 3, 4). These duplications are thought to have arisen from successive unequal recombinations between Alu family repeats. This method of gene amplification is analogous to the Alu-Alu recombinations that cause deletions of the human @globin and low density lipoprotein receptor genes (5, 6). Expression of the GHl gene is controlled by cis and truns factors. The former include the CAT and TATA promoter components located 85 and 30 bp, respectively, upstream from the GHl gene’s origin of transcription. In addition, there are cis sequences that bind the Pit-I transacting factor. Thus, Pit-l factor binds to and activates the promoters of the GHl and PRL genes and also affects differentiation of thyrotropes (7). The frequency of GH deficiency is estimated to range from l/4,000-l/10,000 in various studies (8-11). Most cases are sporadic and are assumed to arise from cerebral insults or defects that include cerebral edema, chromosome anomalies, histiocytosis, infections, radiation, septo-optic dysplasia, trauma, or tumors affecting the hypothalamus or pituitary (1). Magnetic resonance exams detect hypothalamic or pituitary anomalies in about 12% of patients who have isolated GH deficiency (IGHD) (12).

The α-gliadin gene family. II. DNA and protein sequence variation, subfamily structure, and origins of pseudogenes

Abstract: The derived amino-acid sequences of all reported α-gliadin clones are compared and analyzed, and the patterns of sequence change within the α-gliadin family are examined. The most variable sequences are two polyglutamine domains. These two domains are characteristic features of the α-gliadin storage proteins and account for most of the variation in protein size of this otherwise highly conserved protein family. In addition, their encoding DNA sequences form microsatellites. Single-base substitutions in the α-gliadin genes show a preponderance of transitions, including the C to T substitution which contributes to the generation of stop codons, and consequently to the observation that approximately 50% of the α-gliadin genes are pseudogenes. In one unusual gene, a microsatellite has expanded to 321 bp as compared to the normal 36–72 bp, and may result from similar mechanisms that produce polyglutamine-associated genetic diseases in humans. A comparison of the 27 reported sequences show several α-gliadin gene subfamilies, at least some of which are genome specific.

Genomic drift and copy number variation of sensory receptor genes in humans.

Abstract: The number of sensory receptor genes varies extensively among different mammalian species. This variation is believed to be caused partly by physiological requirements of animals and partly by genomic drift due to random duplication and deletion of genes. If the contribution of genomic drift is substantial, each species should contain a significant amount of copy number variation (CNV). We therefore investigated CNVs in sensory receptor genes among 270 healthy humans by using published CNV data. The results indicated that olfactory receptor (OR), taste receptor type 2, and vomeronasal receptor type 1 genes show a high level of intraspecific CNVs. In particular, >30% of the ≈800 OR gene loci in humans were polymorphic with respect to copy number, and two randomly chosen individuals showed a copy number difference of ≈11 in functional OR genes on average. There was no significant difference in the amount of CNVs between functional and nonfunctional OR genes. Because pseudogenes are expected to evolve in a neutral fashion, this observation suggests that functional OR genes also have evolved in a similar manner with respect to copy number change. In addition, we found that the evolutionary change of copy number of OR genes approximately follows the Gaussian process in probability theory, and the copy number divergence between populations has increased with evolutionary time. We therefore conclude that genomic drift plays an important role for generating intra- and interspecific CNVs of sensory receptor genes. Similar results were obtained when all annotated genes were analyzed.

Natural selection on the olfactory receptor gene family in humans and chimpanzees

Abstract: The olfactory receptor (OR) genes constitute the largest gene family in mammalian genomes. Humans have >1,000 OR genes, of which only ∼40% have an intact coding region and are therefore putatively functional. In contrast, the fraction of intact OR genes in the genomes of the great apes is significantly greater (68%–72%), suggesting that selective pressures on the OR repertoire vary among these species. We have examined the evolutionary forces that shaped the OR gene family in humans and chimpanzees by resequencing 20 OR genes in 16 humans, 16 chimpanzees, and one orangutan. We compared the variation at the OR genes with that at intergenic regions. In both humans and chimpanzees, OR pseudogenes seem to evolve neutrally. In chimpanzees, patterns of variability are consistent with purifying selection acting on intact OR genes, whereas, in humans, there is suggestive evidence for positive selection acting on intact OR genes. These observations are likely due to differences in lifestyle, between humans and great apes, that have led to distinct sensory needs.

The human TREM gene cluster at 6p21.1 encodes both activating and inhibitory single IgV domain receptors and includes NKp44.

Abstract: We have characterized a cluster of single immunoglobulin variable (IgV) domain receptors centromeric of the major histocompatibility complex (MHC) on human chromosome 6. In addition to triggering receptor expressed on myeloid cells (TREM)-1 and TREM2, the cluster contains NKp44, a triggering receptor whose expression is limited to NK cells. We identified three new related genes and two gene fragments within a cluster of similar to200 kb. Two of the three new genes lack charged residues in their transmembrane domain tails. Further, one of the genes contains two potential immunotyrosine inhibitory motifs in its cytoplasmic tail, suggesting that it delivers inhibitory signals. The human and mouse TREM clusters appear to have diverged such that there are unique sequences in each species. Finally, each gene in the TREM cluster was expressed in a different range of cell types.