Journal
JOURNAL OF MEDICAL GENETICS
Volume 44, Issue 8, Pages 498-508Publisher
BMJ PUBLISHING GROUP
DOI: 10.1136/jmg.2007.049650
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Funding
- Biotechnology and Biological Sciences Research Council [BB/E024211/1] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
- Biotechnology and Biological Sciences Research Council [BB/E024211/1] Funding Source: researchfish
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Introduction: Microarray gene-expression profiling is a powerful tool for global analysis of the transcriptional consequences of disease phenotypes. Understanding the genetic correlates of particular pathological states is important for more accurate diagnosis and screening of patients, and thus for suggesting appropriate avenues of treatment. As yet, there has been little research describing gene-expression profiling of infertile and subfertile men, and thus the underlying transcriptional events involved in loss of spermatogenesis remain unclear. Here we present the results of an initial screen of 33 patients with differing spermatogenic phenotypes. Methods: Oligonucleotide array expression profiling was performed on testis biopsies for 33 patients presenting for testicular sperm extraction. Significantly regulated genes were selected using a mixed model analysis of variance. Principle components analysis and hierarchical clustering were used to interpret the resulting dataset with reference to the patient history, clinical findings and histological composition of the biopsies. Results: Striking patterns of coordinated gene expression were found. The most significant contains multiple germ cell-specific genes and corresponds to the degree of successful spermatogenesis in each patient, whereas a second pattern corresponds to inflammatory activity within the testis. Smaller-scale patterns were also observed, relating to unique features of the individual biopsies.
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