Identification of novel polymorphisms in the nuclear protein genes and their relationship with human sperm protamine deficiency and severe male infertility.
OBJECTIVE
To screen populations of fertile men, severely infertile men, and infertility patients with aberrations in the protamine-1-to-protamine-2 ratio (P1/P2) for clinically relevant alterations in the P1, P2, transition protein 1 (TP1), and transition protein 2 (TP2) genes.


METHODS
Prospective case-control study.


METHODS
University-based infertility clinic.


METHODS
Ninety-six fertile men, 96 severely infertile men, and 96 infertility patients with aberrations in the sperm P1/P2 ratio.


METHODS
Sperm nuclear protein extraction, gel electrophoresis, and densitometry to evaluate the P1/P2 ratios of infertility patients. DNA extraction, polymerase chain reaction (PCR), and gene sequencing to screen the nuclear protein genes.


METHODS
Sperm P1/P2 ratios and single nucleotide polymorphisms (SNPs) in the sperm nuclear protein genes (P1, P2, TP1, and TP2).


RESULTS
Fifteen SNPs were identified in the nuclear protein genes, 12 of which were previously unreported. Five variants were identified that resulted in amino acid changes (one in P1, one in TP1, and three in TP2). The frequency of the 15 SNPs was similar in protamine-deficient patients, severely infertile patients, and fertile controls.


CONCLUSIONS
A number of SNPs are present in the testis-specific nuclear protein genes. However, the gene variants do not appear to underlie protamine deficiency and severe male infertility.
Aoki
Vincent W
VW
Andrology and IVF Laboratories, University of Utah School of Medicine, Salt Lake City, Utah 84108, USA.
Christensen
Greg L
GL
Atkins
John F
JF
Carrell
Douglas T
DT
D000328:Adult; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D007248:Infertility, Male / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D011446:Prospective Studies; D011479:Protamines / Q000235:genetics*; D013094:Spermatozoa / Q000378:metabolism*; D014589:Utah / Q000453:epidemiology
D009687:Nuclear Proteins; C082073:PRM1 protein, human; D011479:Protamines; C068621:protamine 2