کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2197444 1098884 2009 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
DNA binding activity studies and computational approach of mutant SRY in patients with 46, XY complete pure gonadal dysgenesis
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
DNA binding activity studies and computational approach of mutant SRY in patients with 46, XY complete pure gonadal dysgenesis
چکیده انگلیسی

Mutations of SRY are the cause of 46,XY complete pure gonadal dysgenesis (PGD) in 10–15% of patients. In this study, DNA was isolated and sequenced from blood leukocytes and from paraffin-embedded gonadal tissue in five patients with 46,XY complete PGD. DNA binding capability was analyzed by three different methods. The structure of the full length SRY and its mutant proteins was carried out using a protein molecular model.DNA analysis revealed two mutations and one synonymous polymorphism: in patient #4 a Y96C mutation, and a E156 polymorphism; in patient #5 a S143G mosaic mutation limited to gonadal tissue. We demonstrated, by all methods used, that both mutant proteins reduced SRY DNA binding activity. The three-dimensional structure of SRY suggested that besides the HMG box, the carboxy-terminal region of SRY interacts with DNA.In conclusion, we identified two SRY mutations and a polymorphism in two patients with 46,XY complete PGD, demonstrating the importance of the carboxy-terminal region of SRY in DNA binding activity.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Endocrinology - Volume 299, Issue 2, 27 February 2009, Pages 212–218
نویسندگان
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