Genotype /phenotype correlations in infertility

Project: Research project

Description

DESCRIPTION (provided by applicant): Although infertility affects 10-15% of
all individuals attempting to have children, little is known about the
molecular basis of human puberty and fertility. The long-term goal of this
laboratory is to elucidate the mechanisms underlying the development of normal
puberty and reproductive capability by utilizing patients with infertility who
possess gene mutations. The applicant will study two groups of infertile
patients: those with idiopathic hypogonadotropic hypogonadism (LHH) and those
with normal puberty who have ovulation disorders or sperm abnormalities.
Patients with IHH constitute a severe reproductive-deficient phenotype with
absent puberty, low serum gonadotropins, and infertility. Most infertility
patients have normal puberty, and constitute men with sperm abnormalities
(azoospermia, oligospermia. and/or asthenospermia) or women with ovulation
disorders. The applicant?s overlying hypothesis is that identification of the
genetic mutations in these groups will lead to a better understanding of: 1)
which forms of IHH are hereditary; 2) whether FSH is necessary for normal
sperm concentration and fertility in men, follicular development beyond the
antral stage in women, and for normal androgens in both men and women; and 3)
whether gene mutations affect the function of the encoded proteins. These
hypotheses will be addressed by the following specific aims: Specific Aim 1:
To test candidate genes for linkage and/or mutations in IHH patients; Specific
Aim 2: To screen infertility patients for FSH beta mutations, specifically
those with abnormal semen analyses and those with ovulation disorders, likely
to possess FSH-beta mutations; Specific Aim 3: To create the mutants, express
them in vitro, and determine their effects upon the encoded protein. The
elucidation and analysis of gene mutations in infertile patients will be
important to determine the genetic basis of some forms of infertility and to
determine the underlying mechanisms of puberty and reproduction.
StatusFinished
Effective start/end date8/14/027/31/08

Funding

  • National Institutes of Health: $150,128.00
  • National Institutes of Health: $149,268.00
  • National Institutes of Health: $148,434.00
  • National Institutes of Health: $151,012.00
  • National Institutes of Health: $147,624.00

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Genetic Association Studies
Infertility
Puberty
Mutation
Beta Subunit Follicle Stimulating Hormone
Ovulation
Genes
Fertility
Spermatozoa
Oligospermia
Azoospermia
Semen Analysis
Gonadotropins
Androgens
Reproduction
Proteins
Phenotype
Serum

ASJC

  • Medicine(all)