Species: human
Mutation name: None
type: naturally occurring
fertility: None
Comment: Roy et al. (1995) isolated a gene of which the first 2 coding exons were deleted in approximately 67% of type I spinal muscular atrophy (SMA) chromosomes compared with 2% of non-SMA chromosomes. One model of SMA pathogenesis invokes an inappropriate persistence of motor neuron apoptosis, which is a normally occurring phenomenon in development. Consistent with this hypothesis, the novel gene was labeled 'neuronal apoptosis inhibitory protein' (NAIP) and its function was supported by the finding that it contains domains with sequence similarity to IAPs, baculovirus proteins that inhibit virally induced insect cell apoptosis. The presence of a variable number of copies of truncated and internally deleted versions of the NAIP gene (pseudogenes) was thought to be a possible factor in the genesis of SMA.

Species: human
Mutation name: None
type: naturally occurring
fertility: subfertile
Comment: Array Comparative Genomic Hybridization Profiling Analysis Reveals Deoxyribonucleic Acid Copy Number Variations Associated with Premature Ovarian Failure. Aboura A et al. Introduction: Premature ovarian failure (POF) is defined by amenorrhea of at least 4- to 6-month duration, occurring before 40 yr of age, with two FSH levels in the postmenopausal range. Its etiology remains unknown in more than 80% of cases. Standard karyotypes, having a resolution of 5-10 Mb, have identified critical chromosomal regions, mainly located on the long arm of the X chromosome. Array comparative genomic hybridization (a-CGH) analysis is able to detect submicroscopic chromosomal rearrangements with a higher genomic resolution. We searched for copy number variations (CNVs), using a-CGH analysis with a resolution of approximately 0.7 Mb, in a cohort of patients with POF. Patients and Methods: We prospectively included 99 women. Our study included a conventional karyotype and DNA microarrays comprising 4500 bacterial artificial chromosome clones spread on the entire genome. Results: Thirty-one CNVs have been observed, three on the X chromosome and 28 on autosomal chromosomes. Data have been compared to control populations obtained from the Database of Genomic Variants (http://projects.tcag.ca/variation). Eight statistically significantly different CNVs have been identified in chromosomal regions 1p21.1, 5p14.3, 5q13.2, 6p25.3, 14q32.33, 16p11.2, 17q12, and Xq28. Conclusion: We report the first study of CNV analysis in a large cohort of Caucasian POF patients. In the eight statistically significant CNVs we report, we found five genes (including NAIP) involved in reproduction, thus representing potential candidate genes in POF. The current study along with emerging information regarding CNVs, as well as data on their potential association with human diseases, emphasizes the importance of assessing CNVs in cohorts of POF women.However, we found five genes potentially involved in reproduction in the five remaining CNVs. Among these five genes, two are involved in reproductive diseases (DNAH5 and NAIP), two in reproductive endocrinology (DUSP22 and NUPR1), and one gene in folliculogenesis (AKT1). Table 3, gain of copy number

Species: mouse
Mutation name: None
type: null mutation
fertility: unknown
Comment: The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus. Zhao Y 2011 et al. Inflammasomes are large cytoplasmic complexes that sense microbial infections/danger molecules and induce caspase-1 activation-dependent cytokine production and macrophage inflammatory death. The inflammasome assembled by the NOD-like receptor (NLR) protein NLRC4 responds to bacterial flagellin and a conserved type III secretion system (TTSS) rod component. How the NLRC4 inflammasome detects the two bacterial products and the molecular mechanism of NLRC4 inflammasome activation are not understood. Here we show that NAIP5, a BIR-domain NLR protein required for Legionella pneumophila replication in mouse macrophages, is a universal component of the flagellin-NLRC4 pathway. NAIP5 directly and specifically interacted with flagellin, which determined the inflammasome-stimulation activities of different bacterial flagellins. NAIP5 engagement by flagellin promoted a physical NAIP5-NLRC4 association, rendering full reconstitution of a flagellin-responsive NLRC4 inflammasome in non-macrophage cells. The related NAIP2 functioned analogously to NAIP5, serving as a specific inflammasome receptor for TTSS rod proteins such as Salmonella PrgJ and Burkholderia BsaK. Genetic analysis of Chromobacterium violaceum infection revealed that the TTSS needle protein CprI can stimulate NLRC4 inflammasome activation in human macrophages. Similarly, CprI is specifically recognized by human NAIP, the sole NAIP family member in human. The finding that NAIP proteins are inflammasome receptors for bacterial flagellin and TTSS apparatus components further predicts that the remaining NAIP family members may recognize other unidentified microbial products to activate NLRC4 inflammasome-mediated innate immunity. /////////////////////////