Molecular techniques for finding gene in hypospadias

Hypospadias is a malformation of the genital tract, characterized by incomplete fusion of the urethral folds, abnormal opening of urethra and different degrees of curvature of the penis. Although hypospadias is a common congenital malformation with frequency ranging from 0.4% to 0.8% of male live births, the cause for this malformation is still not understood clearly. A relationship between hypospadias and environmental factors such as low birth weigh, low gestation, parental subfertility and endocrine disruptors has been found in some studies (Kallen and Winberg, 1982, Silver et al, 1999, North and Golding, 2000). Beside environmental factors, several observations suggest that hypospadias is affected by genetic factors. The more severe malformation of the index patient, the higher incidence of hypospadias in the next male siblings. The Mendelian pattern of inheritance (autosomal dominant and autosomal recessive) has been observed in some hypospadias families. Our genome wide linkage analysis study has revealed suggestive linkage at the 4 chromosomal regions: 2q11, 9q22, 10p15 and 10q21 (Frisen et al, 2004). Since both environmental factors and genetic factors have a strong influence on the development of hypospadias, this malformation is considered as complex disease.

The general approaches for finding genes in complex disorder are localization of candidate genes and sequencing the genes that involve in pathogenesis of disease.