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.

A unique form of autosomal dominant cataract explained by gene conversion between β-crystallin B2 and its pseudogene

Abstract: Editor—Using linkage analysis, a large Indian family with autosomal dominant sutural cataract and cerulean opacities was mapped to chromosome 22 and two cosegregating sequence changes (475C→T and 483C→T) were identified in the CRYBB2 gene. The first was previously described in two genetically unrelated families with other inherited forms of cataract. The two sequence alterations are identical to the sequence of the CRYBP1 pseudogene that is 228 kb apart. Furthermore, the pseudogene-like fragment within the CRYBB2 gene is flanked by chromosomal junction sequences. Therefore, we conclude that gene conversion is the most likely mechanism leading to this mutation. Alternatively, dual point mutation would explain our findings. In addition, since the three families with Q155X mutations all show different types of cataract, we conclude that mutant CRYBB2 causes cataract formation but other modifying factors determine the type of cataract. Autosomal dominant congenital cataract (ADCC) is a clinically and genetically heterogeneous group of disorders that cause blindness. More than 13 independent loci have been mapped, and 10 different genes identified so far. Five of them are crystallin genes that are categorised into the α, β, γ, μ, and ζ subgroups. The crystallins constitute the main lens proteins, whereby β-crystallin B2 is the only abundant protein in the adult lens fibre in man.1 2 Causative mutations have been recognised in the α-crystallin A gene (zonular central nuclear cataract),3 the β-crystallin A3/A1 gene (zonular cataracts with sutural opacities),4 the γ-crystallin C gene (Coppock-like cataract),5 and the γ-crystallin D gene (progressive juvenile onset punctate cataract).6These and all other ADCC mutations identified so far are private mutations, with one exception. Litt et al 7 described a nonsense mutation, Q155X, in the β-crystallin B2 gene leading to cerulean cataract. Exactly the same mutation was identified by Gill et al 8 in …

Rapid evolution of goat and sheep globin genes following gene duplication.

Abstract: Statistical analyses of DNA sequences of globin genes (beta A, beta C, and gamma) from goat and sheep (including new sequence information for the second intron of sheep beta A and gamma, kindly provided by A. Davis and A. W. Nienhuis) indicate that the rates of nonsynonymous substitution in these genes have been greatly accelerated following the gene duplication separating gamma and the ancestor of beta A and beta C and the gene duplication separating beta A and beta C. In both cases the acceleration was apparently due to relaxation of purifying selection (functional constraints) rather than advantageous mutations because acceleration occurred only in less important parts of the beta globin chain. The rates of nonsynonymous substitution in these genes are estimated to be about 2.3 x 10(-9) per site per year, which is three times higher than that for the divergence between human beta and mouse beta major globin genes. Our analyses further suggest that the rate of synonymous substitution in functional genes and the rate of substitution in pseudogenes are approximately equal and are between 2.8 x 10(-9) and 5.0 x 10(-9) and that the rate of substitution in introns is about 3.0 x 10(-9). The divergence time between beta A and beta C and that between gamma and the beta A-beta C pair are about 12 and 30 million years, respectively. The proportion of transition mutations is estimated to be 64%, two times higher than expected under random mutation but considerably lower than the 96% estimated for animal mitochondrial DNA.

Genes in a Refined Smith-Magenis Syndrome Critical Deletion Interval on Chromosome 17p11.2 and the Syntenic Region of the Mouse

Abstract: Smith-Magenis syndrome (SMS) is a multiple congenital anomaly/mental retardation syndrome associated with behavioral abnormalities and sleep disturbance. Most patients have the same ∼4 Mb interstitial genomic deletion within chromosome 17p11.2. To investigate the molecular bases of the SMS phenotype, we constructed BAC/PAC contigs covering the SMS common deletion interval and its syntenic region on mouse chromosome 11. Comparative genome analysis reveals the absence of all three ∼200-kb SMS-REP low-copy repeats in the mouse and indicates that the evolution of SMS-REPs was accompanied by transposition of adjacent genes. Physical and genetic map comparisons in humans reveal reduced recombination in both sexes. Moreover, by examining the deleted regions in SMS patients with unusual-sized deletions, we refined the minimal Smith-Magenis critical region (SMCR) to an ∼1.1-Mb genomic interval that is syntenic to an ∼1.0-Mb region in the mouse. Genes within the SMCR and its mouse syntenic region were identified by homology searches and by gene prediction programs, and their gene structures and expression profiles were characterized. In addition to 12 genes previously mapped, we identified 8 new genes and 10 predicted genes in the SMCR. In the mouse syntenic region of the human SMCR, 16 genes and 6 predicted genes were identified. The SMCR is highly conserved between humans and mice, including 19 genes with the same gene order and orientation. Our findings will facilitate both the identification of gene(s) responsible for the SMS phenotype and the engineering of an SMS mouse model.