Human Gene-Centric Databases at the Weizmann Institute of Science: GeneCards, UDB, CroW 21 and HORDE

Chalifa‐Caspi, Vered; Shmueli, Orit; Olender, Tsviya; Lapidot, Michal; Rosen, Naomi; Shmoish, Michael; Peter, Yakov; Glusman, Gustavo; Feldmesser, Ester; Adato, Avital; Peter, Inga; Khen, Miriam; Atarot, Tal; Groner, Yoram; Lancet, Doron

doi:10.1093/nar/gkg050

Cited by 210 publications

(151 citation statements)

References 22 publications

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“…To design the profile HMM for each gene family, a collection of protein sequences from HORDE OLFR database #42 (Safran et al 2003) was used as the training set. The Homo sapiens (human), Pan troglodytes (chimpanzee), Canis familiaris (dog), Monodelphis domestica (gray short-tailed opossum), and Ornithorhynchus anatinus (platypus) complete sets of annotated OR genes were extracted and aligned using ClustalW v2.0 (Larkin et al 2007), and one profile HMM was designed for each of the original 17 OR gene families.…”

Section: Or Family Assignment and Classification Of Retrieved And Ampmentioning

confidence: 99%

Ecological adaptation determines functional mammalian olfactory subgenomes

Hayden¹,

Bekaert²,

Crider³

et al. 2009

Genome Res.

223

307

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The ability to smell is governed by the largest gene family in mammalian genomes, the olfactory receptor (OR) genes. Although these genes are well annotated in the finished human and mouse genomes, we still do not understand which receptors bind specific odorants or how they fully function. Previous comparative studies have been taxonomically limited and mostly focused on the percentage of OR pseudogenes within species. No study has investigated the adaptive changes of functional OR gene families across phylogenetically and ecologically diverse mammals. To determine the extent to which OR gene repertoires have been influenced by habitat, sensory specialization, and other ecological traits, to better understand the functional importance of specific OR gene families and thus the odorants they bind, we compared the functional OR gene repertoires from 50 mammalian genomes. We amplified more than 2000 OR genes in aquatic, semi-aquatic, and flying mammals and coupled these data with 48,000 OR genes from mostly terrestrial mammals, extracted from genomic projects. Phylogenomic, Bayesian assignment, and principle component analyses partitioned species by ecotype (aquatic, semi-aquatic, terrestrial, flying) rather than phylogenetic relatedness, and identified OR families important for each habitat. Functional OR gene repertoires were reduced independently in the multiple origins of aquatic mammals and were significantly divergent in bats. We reject recent neutralist views of olfactory subgenome evolution and correlate specific OR gene families with physiological requirements, a preliminary step toward unraveling the relationship between specific odors and respective OR gene families.

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Section: Or Family Assignment and Classification Of Retrieved And Ampmentioning

confidence: 99%

Ecological adaptation determines functional mammalian olfactory subgenomes

Hayden¹,

Bekaert²,

Crider³

et al. 2009

Genome Res.

223

307

View full text Add to dashboard Cite

show abstract

“…There is also biological plausibility for the 14q and 9q regions to be harbouring new risk genes for hereditary CRC. In particular, it is interesting that the MMR gene, MLH3, is among the 84 protein coding genes that map to the 6.5 Mb region of 14q24.3-q31.1 (Supplementary Table 1) and is among the nine genes in this region that have been annotated in the Genecards database 30 as being altered in CRC (Supplementary Table 2). We also note that of the 152 protein coding genes that map to the 12 Mb region of 9q32-q34.13 (Supplementary Table 3), 22 have been annotated in the Genecards database, 30 as being altered in CRC (Supplementary Table 4) and that this includes three key enzymes in the prostaglandin biosynthesis pathway, COX-1, PTGES and PTGES2.…”

Section: Discussionmentioning

confidence: 99%

Evidence of linkage to chromosomes 10p15.3–p15.1, 14q24.3–q31.1 and 9q33.3–q34.3 in non-syndromic colorectal cancer families

et al. 2011

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Up to 25% of colorectal cancer (CRC) may be caused by inherited genetic variants that have yet to be identified. Previous genome-wide linkage studies (GWLSs) have identified a new loci postulated to contain novel CRC risk genes amongst affected families carrying no identifiable mutations in any of the known susceptibility genes for familial CRC syndromes. To undertake a new GWLS, we recruited members from 54 non-syndromic families from Australia and Spain where at least two first-degree relatives were affected by CRC. We used single-nucleotide polymorphism arrays to genotype 98 concordant affected relative pairs that were informative for linkage analyses. We tested for genome-wide significance (GWS) for linkage to CRC using a quantile statistic method, and we found that GWS was achieved at the 5% level. Independently, using the PSEUDO gene-dropping algorithm, we also found that GWS for linkage to CRC was achieved (P¼0.02). Merlin non-parametric linkage analysis revealed significant linkage to CRC for chromosomal region 10p15.3-p15.1 and suggestive linkage to CRC for regions on 14q and 9q. The 10p15.3-p15.1 has not been reported to be linked to hereditary CRC in previous linkage studies, but this region does harbour the Kruppel-like factor 6 (KLF6) gene that is known to be altered in common CRC. Further studies aimed at localising the responsible genes, and characterising their function will give insight into the factors responsible for susceptibility in such families, and perhaps shed further light on the mechanisms of CRC development.

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“…15 The intact gene and pseudogene polymorphisms were identified from the work of Menashe et al 13,14 and the HORDE database. 15 For each segregating human OR gene, a primer set was designed that could amplify the intact and pseudogene allele, as well as produce an amplified DNA fragment containing the corresponding allele polymorphism. Determination of an individual's genotype is possible, as each primer set was designed so that a unique restriction site is present in the amplified DNA fragment from only one of the two alleles.…”

Section: Primer Designmentioning

confidence: 99%

A Rapid Genotyping Assay for Segregating Human Olfactory Receptor Pseudogenes

Hinkley

Ismaili²

2012

J Biomol Tech

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Variation in odor perception between individuals is initiated by binding of "odorant" molecules to olfactory receptors (ORs) located in the nasal cavity. To determine the mechanism for variation in odor perception, identification of specific ligands for a large number of ORs is required. However, it has been difficult to identify specific ligands, and ligands have been identified for only 2-3% of the hundreds of mammalian ORs. One way to increase the number of identified ligands is to take advantage of Ͼ60 human OR genes that are segregating as a result of a single nucleotide polymorphism, between a functional intact allele and a nonfunctional pseudogene allele. Potential ligands for these ORs can be identified by correlating odor perception of an individual with their genotype [intact/intact (I/I) vs. pseudogene/pseudogene (P/P)] for an OR gene. For this type of study, genotypes must be determined for a large number of individuals. We have developed a PCR-based assay to distinguish between the intact and pseudogene alleles of 49 segregating human OR genes and to determine an individual's genotype for these genes. To facilitate rapid determination of genotypes for a large number of individuals, the assay uses a small number of simple steps and equipment commonly found in most molecular biology and biochemistry laboratories. Although this assay was developed to distinguish between polymorphisms in OR genes, it can easily be adapted for use in distinguishing single nucleotide polymorphisms in any gene or chromosomal locus.

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Human Gene-Centric Databases at the Weizmann Institute of Science: GeneCards, UDB, CroW 21 and HORDE

Cited by 210 publications

References 22 publications

Ecological adaptation determines functional mammalian olfactory subgenomes

Ecological adaptation determines functional mammalian olfactory subgenomes

Evidence of linkage to chromosomes 10p15.3–p15.1, 14q24.3–q31.1 and 9q33.3–q34.3 in non-syndromic colorectal cancer families

A Rapid Genotyping Assay for Segregating Human Olfactory Receptor Pseudogenes

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