Members of the olfactory receptor gene family are contained in large blocks of DNA duplicated polymorphically near the ends of human chromosomes

Trask, Barbara J.; Friedman, Cynthia; Martin-Gallardo, Antonia; Rowen, Lee; Akinbami, Carolyn; Blankenship, John W.; Collins, Colin C.; Giorgi, Dominique; Iadonato, Shawn P.; Johnson, Forrester; Kuo, Wen Lin; Massa, Hillary F.; Morrish, Tammy A.; Naylor, Susan L.; Nguyen, Oanh; Rouquier, Sylvie; Smith, T. M. F.; Wong, D.; Youngblom, Janey; Engh, Ger van den

doi:10.1093/hmg/7.1.13

Cited by 202 publications

(176 citation statements)

References 54 publications

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“…Almost 80% of the ORs are organized in clusters of six or more genes [9,10]. This is in good agreement with previous fluorescence in situ hybridization (FISH) experiments and sequencing data [7,13,14]. …”

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confidence: 84%

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DEFOG: A Practical Scheme for Deciphering Families of Genes

et al. 2002

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We developed a novel efficient scheme, DEFOG (for "deciphering families of genes"), for determining sequences of numerous genes from a family of interest. The scheme provides a powerful means to obtain a gene family composition in species for which high-throughput genomic sequencing data are not available. DEFOG uses two key procedures. The first is a novel algorithm for designing highly degenerate primers based on a set of known genes from the family of interest. These primers are used in PCR reactions to amplify the members of the gene family. The second combines oligofingerprinting of the cloned PCR products with clustering of the clones based on their fingerprints. By selecting members from each cluster, a low-redundancy clone subset is chosen for sequencing. We applied the scheme to the human olfactory receptor (OR) genes. OR genes constitute the largest gene superfamily in the human genome, as well as in the genomes of other vertebrate species. DEFOG almost tripled the size of the initial repertoire of human ORs in a single experiment, and only 7% of the PCR clones had to be sequenced. Extremely high degeneracies, reaching over a billion combinations of distinct PCR primer pairs, proved to be very effective and yielded only 0.4% nonspecific products. characterized in rat a decade ago [2] and have since been detected in many vertebrate species [reviewed in 6]. So far, about 3000 OR genes and pseudogenes are known in 24 vertebrate species [7][8][9][10][11][12]. They are divided into 32 distinct families based on phylogenetic analysis [8].Roughly 900 OR coding sequences were found in the first draft of the human genome [9,10]. As predicted [7,13], between 53% and 63% of them have frame disruptions and are therefore considered as pseudogenes. OR genes are found on almost all human chromosomes except chromosome 20 and Y [7,9,10,13,14]. Almost 80% of the ORs are organized in clusters of six or more genes [9,10]. This is in good agreement with previous fluorescence in situ hybridization (FISH) experiments and sequencing data [7,13,14]. 296Article doi:10.1006/geno.2002.6830, available online at http://www.idealibrary.com on IDEAL The coding region of OR genes spans approximately 1 kb. This region lacks introns [2,13] and is preceded by a large intron and several short noncoding exons [16][17][18][19][20]. Inside the coding region there are several conserved segments [21] that allow easy amplification of the intronless coding region from genomic DNA by PCR assay. The PCR product is termed the "olfactory receptor sequence tag" (OST) [7].We developed and experimentally tested a practical scheme for deciphering families of genes (DEFOG). The scheme provides a powerful means to obtain a sequence composition of a gene family in species for which high-throughput genomic sequencing data are unavailable. To validate DEFOG, we tested it on the human OR gene superfamily. Starting with a limited number of human ORs, it almost tripled the size of this set in a single experiment. We suggest that DEFOG can be successfully appli...

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supporting

confidence: 84%

“…As predicted [7,13], between 53% and 63% of them have frame disruptions and are therefore considered as pseudogenes. OR genes are found on almost all human chromosomes except chromosome 20 and Y [7,9,10,13,14]. Almost 80% of the ORs are organized in clusters of six or more genes [9,10].…”

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confidence: 99%

DEFOG: A Practical Scheme for Deciphering Families of Genes

et al. 2002

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“…The map comprises ~2. 6 Mbp of sequence present in two or more of 33 human subtelomeres (including three allelic pairs). The seven completely sequenced subtelomeres in the set are bounded distally by 0.5-2.4 kbp of various tandemly repeated units 13 called telomere-associated repeats (TAR1) and a short sample of the native telomeric arrays 14 .…”

Section: Complex Inter-related Structuresmentioning

confidence: 99%

Human subtelomeres are hot spots of interchromosomal recombination and segmental duplication

Linardopoulou

Williams

Fan

et al. 2005

Nature

376

415

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Human subtelomeres are polymorphic patchworks of inter-chromosomal segmental duplications at the ends of chromosomes. We provide evidence here that these patchworks arose recently through repeated translocations between chromosome ends. We assess the relative contribution of the major modes of ectopic DNA repair to the formation of subtelomeric duplications and find that nonhomologous end-joining predominates. Once subtelomeric duplications arise, they are prone to homology-based sequence transfers as evidenced by incongruent phylogenetic relationships of neighboring sections. Inter-chromosomal recombination of subtelomeres is a potent force for recent change. Cytogenetic and sequence analyses reveal that pieces of the subtelomeric patchwork changed location and copy number during primate evolution with unprecedented frequency. Half of known subtelomeric sequence formed recently through human-specific sequence transfers and duplications. Subtelomeric dynamics result in a gene-duplication rate significantly higher than the genome average and could have both advantageous and pathological consequences in human biology. More generally, our analyses suggest an evolutionary cycle between segmental polymorphisms and genome rearrangements.The human genome contains an abundance of large DNA segments that duplicated during the last 40 million years 1,2 . These segmental duplications (SDs) represent ≥5% of the genome 2 and are found frequently near centromeres and telomeres 3 . SDs are emerging as significant factors in chromosomal rearrangements leading to disease 4 and rapid gene innovation 2 , but the mechanisms by which they form are not well understood. Here, we focus on the unusually dense concentrations of inter-chromosomal SDs comprising human subtelomeres, which form the transition zones between chromosome-specific sequence and the arrays of telomeric repeats capping each chromosomal end. Previous cytogenetic studies showed that human subtelomeres are strikingly polymorphic in content -large segments can be present in or absent from normal alleles 5 -and that copy number of subtelomeric segments can vary among higher primates 6-9 . This natural plasticity combined with documented expression of several human subtelomeric genes 10,11 suggests that the evolutionary dynamics of subtelomeric regions could contributeCorrespondence and requests for materials should be addressed to B.J.T. (e-mail: btrask@fhcrc.org Complex inter-related structuresOur "paralogy map" of subtelomeric SDs (Fig. 1, Table S1) uses all finished sequences of genomic clones submitted to GenBank before April 2003. The map comprises ~2.6 Mbp of sequence present in two or more of 33 human subtelomeres (including three allelic pairs). The seven completely sequenced subtelomeres in the set are bounded distally by 0.5-2.4 kbp of various tandemly repeated units 13 called telomere-associated repeats (TAR1) and a short sample of the native telomeric arrays 14 . Numerous degenerate telomere-like repeats and TAR1 elements are also situated at varying...

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“…However, apart from this observation, there is no direct evidence for SD at telomeres in any organism. Indirectly, several observations might be attributable to competition among driving telomeres, such as a rapid diversification between human and chimpanzee telomeric regions (Trask et al, 1998), a high degree of human subtelomere sequence diversity (Mefford and Trask, 2002) and recurrent selective sweeps in human subtelomeric regions (Hellmann et al, 2008). Also, given that telomere drive would cause a similar genetic conflict to that caused by driving centromeres, it is interesting that there is evidence for rapid evolution of telomere-binding proteins in Drosophila (Anderson et al, 2009).…”

Section: Drive At Telomeres?mentioning

confidence: 99%

Segregation distortion in chicken and the evolutionary consequences of female meiotic drive in birds

et al. 2010

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As all four meiotic products give rise to sperm in males, female meiosis result in a single egg in most eukaryotes. Any genetic element with the potential to influence chromosome segregation, so that it is preferentially included in the egg, should therefore gain a transmission advantage; a process termed female meiotic drive. We are aware of two chromosomal components, centromeres and telomeres, which share the potential to influence chromosome movement during meioses and make the following predictions based on the presence of female meiotic drive: (1) centromere-binding proteins should experience rapid evolution as a result of a conflict between driving centromeres and the rest of the genome; and (2) segregation patterns should be skewed near centromeres and telomeres. To test these predictions, we first analyze the molecular evolution of seven centromere-binding proteins in nine divergent bird species.We find strong evidence for positive selection in two genes, lending support to the genomic conflict hypothesis. Then, to directly test for the presence of segregation distortion, we also investigate the transmission of B9000 single-nucleotide polymorphisms in 197 chicken families. By simulating fair Mendelian meioses, we locate chromosomal regions with statistically significant transmission ratio distortion. One region is located near the centromere on chromosome 1 and a second region is located near the telomere on the parm of chromosome 1. Although these observations do not provide conclusive evidence in favour of the meiotic drive/ genome conflict hypothesis, they do lend support to the hypothesis that centromeres and telomeres drive during female meioses in chicken.

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Members of the olfactory receptor gene family are contained in large blocks of DNA duplicated polymorphically near the ends of human chromosomes

Cited by 202 publications

References 54 publications

DEFOG: A Practical Scheme for Deciphering Families of Genes

DEFOG: A Practical Scheme for Deciphering Families of Genes

Human subtelomeres are hot spots of interchromosomal recombination and segmental duplication

Segregation distortion in chicken and the evolutionary consequences of female meiotic drive in birds

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