Identified in a GWAS analysis of Chinese men with non-obstructive azoospermia (FBrf0232613), the human gene SNRPA1 is proposed as a candidate gene for involvement in human male fertility. SNRPA1 encodes one of the protein constituents of the U2 snRNP (small nuclear ribonucleoprotein) component of the spliceosome. There is a single fly ortholog, U2A, for which a classical loss-of-function alleles and RNAi-targeting constructs have been generated.
An amorphic mutation of Dmel\U2A is a recessive lethal. Targeted loss of U2A during spermatogenesis results in accumulation of mitotic spermatogonia that fail to differentiate into spermatocytes and mature sperm.
UAS constructs of the human Hsap\SNRPA1 have been introduced into flies, including wild-type and mutant forms. Heterologous rescue (functional complementation) has been demonstrated: ubiquitous expression of wild-type Hsap\SNRPA1 rescues the lethal phenotype of a U2A null mutant. Variant(s) implicated in human disease tested (as transgenic human gene, SNRPA1): the Q148R variant form has been introduced into flies; this mutant form acts as a dominant negative in flies, disrupting spermatogenesis when expressed in germline cells.
Genetic and physical interactions of Dmel\U2A have been described; see below and in the U2A gene report.
[updated Jul. 2017 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.
Based on phenotype in Drosophila (targeted loss of Dmel\U2A during spermatogenesis results in accumulation of mitotic spermatogonia that fail to differentiate into spermatocytes and mature sperm), it is postulated spliceosome defects and resulting defects in mRNA processing may contribute to nonobstructive azoospermia.
SNRPA1 encodes one of the specific protein constituents of the U2 snRNP (small nuclear ribonucleoprotein) component of the slicesome. [from MIM:603521; 2016.11.03]
One to one: 1 human to 1 Drosophila.
Ortholog of human SNRPA1 (1 Drosophila to 1 human). Dmel\U2A shares 52% identity and 67% similarity with human SNRPA1.
