Multiple haplotype-resolved genomes reveal population patterns of gene and protein diplotypes.

To fully understand human biology and link genotype to phenotype, the phase of DNA variants must be known. Here we present a comprehensive analysis of haplotype-resolved genomes to assess the nature and variation of haplotypes and their pairs, diplotypes, in European population samples. We use a set of 14 haplotype-resolved genomes generated by fosmid clone-based sequencing, complemented and expanded by up to 372 statistically resolved genomes from the 1000 Genomes Project.

Association of polymorphisms of the cannabinoid receptor (CNR1) and fatty acid amide hydrolase (FAAH) genes with heroin addiction: impact of long repeats of CNR1.

Alterations in expression of a cannabinoid receptor (CNR1, CB1), and of fatty acid amide hydrolase (FAAH) that degrades endogenous ligands of CB1, may contribute to the development of addiction. The 385C>A in the FAAH gene and six polymorphisms of CNR1 were genotyped in former heroin addicts and control subjects (247 Caucasians, 161 Hispanics, 179 African Americans and 19 Asians). In Caucasians, long repeats (>or=14) of 18087-18131(TAA)(8-17) were associated with heroin addiction (P=0.

The single nucleotide polymorphism A118G alters functional properties of the human mu opioid receptor.

The most common single nucleotide polymorphism in the coding region of the human mu opioid receptor gene is the A118G variant, an adenine to guanine transition at nucleotide position 118 of the coding sequence of the gene. This polymorphism codes for an asparagine to aspartic acid substitution at amino acid 40 in the amino-terminus, thereby removing a potential extracellular glycosylation site. Using in vitro cellular expression assays, this variant has been reported to change binding of the endogenous agonist beta-endorphin and signaling of the receptor following binding of beta-endorphin.

Genetic variation and pharmacogenomics: concepts, facts, and challenges.

The analysis of genetic variation in candidate genes is an issue of central importance in pharmacogenomics. The specific approaches taken will have a critical impact on the successful identification of disease genes, the molecular correlates of drug response, and the establishment of meaningful relationships between genetic variants and phenotypes of biomedical and pharmaceutical importance in general. Against a historical background, this article distinguishes different approaches to candidate gene analysis, reflecting different stages in human genome research.

A truncated delta opioid receptor, spontaneously produced in human but not rat neuroblastoma cells, interferes with signaling of the full-length receptor.

In addition to the established human delta opioid receptor SH-SY5Y neuroblastoma cells produce an atypical, shorter, form of this receptor which is predicted to lack the third intracellular domain. Hence it will be referred to as hdelta(deltaICD3). Notably, in unaltered human brain tissue only the established ('wild type') delta receptor was detected.