RESUMO
This article provides nomenclature recommendations developed by an international workgroup to increase transparency and standardization of pharmacogenetic (PGx) result reporting. Presently, sequence variants identified by PGx tests are described using different nomenclature systems. In addition, PGx analysis may detect different sets of variants for each gene, which can affect interpretation of results. This practice has caused confusion and may thereby impede the adoption of clinical PGx testing. Standardization is critical to move PGx forward.
Assuntos
Alelos , Testes Genéticos/normas , Farmacogenética/normas , Terminologia como Assunto , Genes , Testes Genéticos/tendências , Variação Genética , Humanos , Farmacogenética/tendências , Medicina de PrecisãoAssuntos
Acetiltransferases/classificação , Proteínas de Ligação a DNA/classificação , Histona-Lisina N-Metiltransferase/metabolismo , Histonas/metabolismo , Metiltransferases/classificação , Proteínas de Neoplasias/metabolismo , Terminologia como Assunto , Animais , Proteínas de Ligação a DNA/metabolismo , HumanosRESUMO
To unravel the system of epigenetic control of transcriptional regulation is a fascinating and important scientific pursuit. Surprisingly, recent successes in gene identification using high-throughput sequencing strategies showed that, despite their ubiquitous role in transcriptional control, dysfunction of chromatin-modifying enzymes can cause very specific human developmental phenotypes. An intriguing example is the identification of de novo dominant mutations in MLL2 as a cause of Kabuki syndrome, a well-known congenital syndrome that is associated with a very recognizable facial gestalt. However, the existing confusion in the nomenclature of the human and mouse MLL gene family impedes correct interpretation of scientific findings for these genes and their encoded proteins. This Review aims to point out this nomenclature pitfall, to explain its historical background, and to promote an unequivocal nomenclature system for chromatin-modifying enzymes as proposed by Allis et al. (2007).
Assuntos
Proteínas de Ligação a DNA/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Histonas/metabolismo , Proteínas de Neoplasias/metabolismo , Terminologia como Assunto , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/patologia , Animais , Proteínas de Ligação a DNA/genética , Face/anormalidades , Doenças Hematológicas/patologia , Histona-Lisina N-Metiltransferase/genética , Humanos , Mutação , Proteínas de Neoplasias/genética , Síndrome , Doenças Vestibulares/patologiaRESUMO
Bardet-Biedl syndrome (BBS) is a clinically and genetically heterogeneous autosomal recessive disorder characterized by retinitis pigmentosa, polydactyly, obesity, hypogenitalism, mental retardation, and renal anomalies. To detect linkage to BBS loci, 29 BBS families, of mixed but predominantly European ethnic origin, were typed with 37 microsatellite markers on chromosomes 2, 3, 11, 15, 16, and 17. The results show that an estimated 36-56% of the families are linked to the 11q13 chromosomal site (BBS1) previously described by M. Leppert et al. (1994, Nature Genet. 7, 108-112), with the gene order cen-D11S480-5 cM-BBS1-3 cM-D11S913/D11S987-qter. A further 32-35% of the families are linked to the BBS4 locus, reported by R. Carmi et al. (1995, Hum. Mol. Genet. 4, 9-13) in chromosomal region 15q22.3-q23, with the gene order cen-D15S125-5 cM-BBS4-2 cM-D15S131/D15S204-qter. Three consanguineous BBS families are homozygous for three adjacent chromosome 15 markers, consistent with identity by descent for this region. In one of these families haplotype analysis supports a localization for BBS4 between D15S131 and D15S114, a distance of about 2 cM. Weak evidence of linkage to the 16q21 (BBS2) region reported by A. E. Kwitek-Black et al. (1993, Nature Genet. 5, 392-396) was observed in 24-27% of families with the gene order cen-D16S408-2 cM-BBS2-5 cM-D16S400. A fourth group of families, estimated at 8%, are unlinked to all three of the above loci, showing that at least one other BBS locus remains to be found. No evidence of linkage was found to markers on chromosome 3, corresponding to the BBS3 locus, reported by V. C. Sheffield et al. (1994, Hum. Mol. Genet. 3, 1331-1335), or on chromosome 2 or 17, arguing against the involvement of a BBS locus in a patient with a t(2;17) translocation.
Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 15/genética , Cromossomos Humanos Par 16/genética , Ligação Genética , Mapeamento Cromossômico , Feminino , Genes Recessivos , Marcadores Genéticos , Haplótipos , Humanos , Hipogonadismo/genética , Deficiência Intelectual/genética , Escore Lod , Masculino , Obesidade/genética , Linhagem , Polidactilia/genética , Retinose Pigmentar/genética , SíndromeRESUMO
We describe a detailed physical map of human chromosome 11, extending from the distal part of p13 through the entirety of p14 to proximal p15.1. The primary level of mapping is based on chromosome breakpoints that divide the region into 20 intervals. At higher resolution YACs cover approximately 12 Mb of the region, and in many places overlapping cosmids are ordered in contiguous arrays. The map incorporates 18 known genes, including precise localization of the GTF2H1 gene encoding the 62-kDa subunit of TFIIH. We have also localized four expressed sequences of unknown function. The physical map incorporates genetic markers that allow relationships between physical and genetic distance to be examined, and similarly includes markers from a radiation hybrid map of 11. The cytogenetic location of cosmids has been examined on high-resolution banded chromosomes by fluorescence in situ hybridization, and FLpter values have been determined. The map therefore fully integrates physical, genic, genetic, and cytogenetic information and should provide a robust framework for the rapid and accurate assignment of new markers at a high level of resolution in this region of 11p.
