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From the moment of conception, we begin to age. A decay of cellular structures, gene regulation, and DNA sequence ages cells and organisms. DNA methylation patterns change with increasing age and contribute to age related disease. Here we identify 88 sites in or near 80 genes for which the degree of cytosine methylation is significantly correlated with age(More)
The central dogma of mammalian brain sexual differentiation has contended that sex steroids of gonadal origin organize the neural circuits of the developing brain. Recent evidence has begun to challenge this idea and has suggested that, independent of the masculinizing effects of gonadal secretions, XY and XX brain cells have different patterns of gene(More)
Allele-specific DNA methylation (ASM) is a hallmark of imprinted genes, but ASM in the larger nonimprinted fraction of the genome is less well characterized. Using methylation-sensitive SNP analysis (MSNP), we surveyed the human genome at 50K and 250K resolution, identifying ASM as recurrent genotype call conversions from heterozygosity to homozygosity when(More)
Wnt-4, a member of the Wnt family of locally acting secreted growth factors, is the first signaling molecule shown to influence the sex-determination cascade. In mice, a targeted deletion of Wnt-4 causes the masculinization of XX pups. Therefore, WNT-4, the human homologue of murine Wnt-4, is a strong candidate gene for sex-reversal phenotypes in humans. In(More)
The classic view of brain sexual differentiation and behavior is that gonadal steroid hormones act directly to promote sex differences in neural and behavioral development. In particular, the actions of testosterone and its metabolites induce a masculine pattern of brain development, while inhibiting feminine neural and behavioral patterns of(More)
Disorders of sex development (DSD), ranging in severity from mild genital abnormalities to complete sex reversal, represent a major concern for patients and their families. DSD are often due to disruption of the genetic programs that regulate gonad development. Although some genes have been identified in these developmental pathways, the causative mutations(More)
IMPORTANCE Cerebellar ataxias are a diverse collection of neurologic disorders with causes ranging from common acquired etiologies to rare genetic conditions. Numerous genetic disorders have been associated with chronic progressive ataxia and this consequently presents a diagnostic challenge for the clinician regarding how to approach and prioritize genetic(More)
Disorders in human sex determination cause defects in gonadal function and can result in a spectrum of abnormalities in the internal and external genitalia, ranging from relatively mild sexual ambiguities to complete sex reversal. Several genes involved in sex determination have been validated in humans, and activities of their gene products are being(More)
The fear of experiencing discrimination often provokes symptoms of psychological distress. One coping resource is positive identification with one's social group-known as collective self-esteem. This preliminary study investigated whether collective self-esteem was related to fears regarding a transsexual identity and psychological distress among 53(More)
The human testis-determining factor resides within a 35-kilobase (kb) region of the Y chromosome immediately adjacent to the pseudoautosomal boundary. A candidate gene for human sex determination (SRY) was isolated in this region. Here, we describe a study of 25 cases of XY females with pure gonadal dysgenesis for mutations on the Y chromosome short arm,(More)