Article

Human olfaction: from genome variation to phenotypic diversity

Department of Molecular Genetics and the Crown Human Genome Center, Weizmann Institute of Science, Rehovot 76100, Israel.
Trends in Genetics (Impact Factor: 11.6). 05/2009; 25(4):178-84. DOI: 10.1016/j.tig.2009.02.002
Source: PubMed

ABSTRACT The sense of smell is a complex molecular device, encompassing several hundred olfactory receptor proteins (ORs). These receptors, encoded by the largest human gene superfamily, integrate odorant signals into an accurate 'odor image' in the brain. Widespread phenotypic diversity in human olfaction is, in part, attributable to prevalent genetic variation in OR genes, owing to copy number variation, deletion alleles and deleterious single nucleotide polymorphisms. The development of new genomic tools, including next generation sequencing and CNV assays, provides opportunities to characterize the genetic variations of this system. The advent of large-scale functional screens of expressed ORs, combined with genetic association studies, has the potential to link variations in ORs to human chemosensory phenotypes. This promises to provide a genome-wide view of human olfaction, resulting in a deeper understanding of personalized odor coding, with the potential to decipher flavor and fragrance preferences.

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Available from: Yehudit Hasin-Brumshtein, Aug 15, 2014
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    • "Thus the possible role of sex in CNV among olfactory receptor (OR) gene family was investigated. OR genes (Buck and Axel, 1991; Rouquier et al., 1998) comprise the largest gene family in the human genome, with nearly 900 members (Glusman et al., 2001; Hasin-Brumshtein et al., 2009) and also have been extensively studied, with regard to CNV (Trask et al., 1998; Waszak et al., 2010). OR gene family is also well-known to have a large number of pseudogenes (about 50%) among its members (Glusman et al., 2001). "
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    ABSTRACT: Gender plays a pivotal role in the human genetic identity and is also manifested in many genetic disorders particularly mental retardation. In this study its effect on copy number variation (CNV), known to cause genetic disorders was explored. As the olfactory receptor (OR) repertoire comprises the largest human gene family, it was selected for this study, which was carried out within and between three populations, derived from 150 individuals from the 1000 Genome Project. Analysis of 3872 CNVs detected among 791 OR loci, in which 307 loci showed CNV, revealed the following novel findings: Sex bias in CNV was significantly more prevalent in uncommon than common CNV variants of OR pseudogenes, in which the male genome showed more CNVs; and in one-copy number loss compared to complete deletion of OR pseudogenes; both findings implying a more recent evolutionary role for gender. Sex bias in copy number gain was also detected. Another novel finding was that the observed six bias was largely dependent on ethnicity and was in general absent in East Asians. Using a CNV public database for sick children (ISCA) the application of these findings for improving clinical molecular diagnostics is discussed by showing an example of sex bias in CNV among kids with autism. Additional clinical relevance is discussed, as the most polymorphic CNV-enriched OR cluster in the human genome, located on chr 15q11.2, is found near the PWS/AS bi-directionally imprinted region associated with two well-known mental retardation syndromes. As olfaction represents the primitive cognition in most mammals, arguably in competition with the development of a larger brain, the extensive retention of OR pseudogenes in females of this study, might point to a parent-of-origin indirect regulatory role for OR pseudogenes in the embryonic development of human brain. Thus any perturbation in the temporal regulation of olfactory system could lead to developmental delay disorders including mental retardation.
    Frontiers in Genetics 03/2013; 4:32. DOI:10.3389/fgene.2013.00032
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