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.

Genomic structure of growth hormone genes in chinook salmon (Oncorhynchus tshawytscha): presence of two functional genes, GH-I and GH-II, and a male-specific pseudogene, GH-Ψ

Abstract: Two chinook salmon (Oncorhynchus tshawytscha) growth hormone genes (a functional GH-I gene and a pseudogene, GH-ψ) were isolated and characterized. The GH-I gene sequence consists of 1.9 kb of 5′-flanking sequence, 4.1 kb of transcribed region, and 64 bp of 3′-flanking sequence, and contains 6 exons and 5 introns. The pseudogene, GH-ψ, spanning 4.1 kb, has a similar structure as the GH-I gene. However, it has one wrong splicing sequence at the intron 1/exon 2 junction, one premature termination codon in exon 5, and a deletion in the last half of exon 5 and the first part of intron 5. In addition to GH-I gene and GH-ψ, a third GH gene, GH-II, was identified by the polymerase chain reaction (PCR) and subsequently shown to be the second functional GH-II gene. To study the linkage arrangement of these three GH genes, 50 unrelated chinook salmon (25 males and 25 females) and one chinook salmon family were analyzed by PCR. The results showed that GH-ψ exists only in males and that it segregates from fa...

Recommended nomenclature for five mammalian carboxylesterase gene families: Human, mouse, and rat genes and proteins

Abstract: Mammalian carboxylesterase (CES or Ces) genes encode enzymes that participate in xenobiotic, drug, and lipid metabolism in the body and are members of at least five gene families. Tandem duplications have added more genes for some families, particularly for mouse and rat genomes, which has caused confusion in naming rodent Ces genes. This article describes a new nomenclature system for human, mouse, and rat carboxylesterase genes that identifies homolog gene families and allocates a unique name for each gene. The guidelines of human, mouse, and rat gene nomenclature committees were followed and “CES” (human) and “Ces” (mouse and rat) root symbols were used followed by the family number (e.g., human CES1). Where multiple genes were identified for a family or where a clash occurred with an existing gene name, a letter was added (e.g., human CES4A; mouse and rat Ces1a) that reflected gene relatedness among rodent species (e.g., mouse and rat Ces1a). Pseudogenes were named by adding “P” and a number to the human gene name (e.g., human CES1P1) or by using a new letter followed by ps for mouse and rat Ces pseudogenes (e.g., Ces2d-ps). Gene transcript isoforms were named by adding the GenBank accession ID to the gene symbol (e.g., human CES1_AB119995 or mouse Ces1e_BC019208). This nomenclature improves our understanding of human, mouse, and rat CES/Ces gene families and facilitates research into the structure, function, and evolution of these gene families. It also serves as a model for naming CES genes from other mammalian species.

Steroid 21-hydroxylase deficiency: two additional mutations in salt-wasting disease and rapid screening of disease-causing mutations

Abstract: A method for genetic diagnosis of steroid 21-hydroxylase deficiency was developed based on allele-specific PCR. With this approach, genotyping of fourteen mutations and diagnosis of homozygous gene deletions can be performed within hours from tissue sampling. One patient with salt-wasting disease had normal genotype at all positions screened. DNA sequencing revealed two novel mutations, a G to C transversion at the conserved splice donor site of intron 7 and a TGG to TAG nonsense mutation at Trp 406 in exon 9. Allele-specific PCR was established also for these mutations and used to screen for their presence in the pseudogene. However, the two novel mutations were not found in at least 34 pseudogenes.

Rates of nuclear and cytoplasmic mitochondrial DNA sequence divergence in mammals.

Abstract: Differential rates of nucleotide substitution among different gene segments and between distinct evolutionary lineages is well documented among mitochondrial genes and is likely a consequence of locus-specific selective constraints that delimit mutational divergence over evolutionary time. We compared sequence variation of 18 homologous loci (15 coding genes and 3 parts of the control region) among 10 mammalian mitochondrial DNA genomes which allowed us to describe different mitochondrial evolutionary patterns and to produce an estimation of the relative order of gene divergence. The relative rates of divergence of mitochondrial DNA genes in the family Felidae were estimated by comparing their divergence from homologous counterpart genes included in nuclear mitochondrial DNA (Numt, pronounced "new might"), a genomic fossil that represents an ancient transfer of 7.9 kb of mitochondrial DNA to the nuclear genome of an ancestral species of the domestic cat (Felis catus). Phylogenetic analyses of mitochondrial (mtDNA) sequences with multiple outgroup species were conducted to date the ancestral node common to the Numt and the cytoplasmic (Cymt) mtDNA genes and to calibrate the rate of sequence divergence of mitochondrial genes relative to nuclear homologous counterparts. By setting the fastest substitution rate as strictly mutational, an empirical "selective retardation index" is computed to quantify the sum of all constraints, selective and otherwise, that limit sequence divergence of mitochondrial gene sequences over time.

Association of the NPAS3 gene and five other loci with response to the antipsychotic iloperidone identified in a whole genome association study.

Abstract: A whole genome association study was performed in a phase 3 clinical trial conducted to evaluate a novel antipsychotic, iloperidone, administered to treat patients with schizophrenia. Genotypes of 407 patients were analyzed for 334,563 single nucleotide polymorphisms (SNPs). SNPs associated with iloperidone efficacy were identified within the neuronal PAS domain protein 3 gene (NPAS3), close to a translocation breakpoint site previously observed in a family with schizophrenia. Five other loci were identified that include the XK, Kell blood group complex subunit-related family, member 4 gene (XKR4), the tenascin-R gene (TNR), the glutamate receptor, inotropic, AMPA 4 gene (GRIA4), the glial cell line-derived neurotrophic factor receptor-alpha2 gene (GFRA2), and the NUDT9P1 pseudogene located in the chromosomal region of the serotonin receptor 7 gene (HTR7). The study of these polymorphisms and genes may lead to a better understanding of the etiology of schizophrenia and of its treatment. These results provide new insight into response to iloperidone, developed with the ultimate goal of directing therapy to patients with the highest benefit-to-risk ratio.