Identified in a GWAS analysis of Chinese men with non-obstructive azoospermia (FBrf0227519), the human gene NDST1 is proposed as a candidate gene for involvement in human male fertility. NDST1 catalyzes both the N-deacetylation and the N-sulfation of heparan sulfate glycosaminoglycans; it is a transmembrane protein that resides in the Golgi apparatus. There is a single fly ortholog, sfl, for which loss-of-function alleles, RNAi-targeting constructs and an allele caused by insertional mutagenesis have been generated. Dmel\sfl is also orthologous to human genes NDST2, NDST3, AND NDST4. The NDST1 gene has also been implicated in an inherited form of mental retardation, MRT46 (MIM:616116).
The NDST1 gene has not been introduced into flies.
In Drosophila, tissue-specific knockdown of sfl using GAL4/UAS-RNAi results in reduced male fertility; functional sfl is required in the somatic cells of the testis for normal fertility. Systemic knockdown typically results in lethaliy during the pupal stage. Genetic interactions of Dmel\sfl have been characterized; see the gene report for that gene.
[updated Apr. 2016 by FlyBase; FBrf0222196]
Non-obstructive azoospermia (NOA) is defined as absence of any measurable level of sperm in semen, resulting from a defect in the production of spermatozoa in the testes. [from MedGen, Non-obstructive azoospermia; MedGen UID: 866757]
Non-obstructive azoospermia (NOA), or failure of spermatogenesis within the testis, is diagnosed in approximately 10% of infertile men. NOA may be due to a lack of appropriate stimulation by gonadotropins, in which case hormonal therapy is usually effective. A larger category of non-obstructive azoospermia consists of men with an intrinsic testicular impairment. In these cases, the primary approach is to improve the quantity and quality of sperm retrieved from the testis for use for in vitro fertilization (Kumar, 2013; PMCID:PMC3583162).
Observation of non-obstructive azoospermia (NOA).
Locus identified in a genome-wide association study (GWAS) of non-obstructive azoospermia in Chinese men.
NDST1 is a member of the heparan sulfate/heparin GlcNAc N-deacetylase/N-sulfotransferase family, involved in the biosynthesis of heparan sulfate proteoglycans. The NDST1 enzyme is a type II transmembrane protein that resides in the Golgi apparatus. [from Gene Cards, NDST1; 2016.04.07]
Many to one: 4 human to 1 Drosophila; additional high-scoring human orthologous genes are NDST2, NDST3, and NDST4; one low-scoring ortholog also exists.
Ortholog of human genes NDST1, NDST2, NDST3, AND NDST4 (1 Drosophila to 4 human). Dmel\sfl shares 53-55% identity and 70-71% similarity with the human genes.
