The homosexual orientation and investigations about the existence of components biological and genetics determinants

The male and female homosexual orientation has substantial prevalence in humans and can be explained by determinants of various levels: biological, genetic, psychological, social and cultural. However, the biological and genetic evidence have been the main hypotheses tested in scientific research in the world. This article aims to review research studies about the existence of genetic and biological evidence that determine homosexual orientation. Was conducted a review of the literature, using the database MedLine/PubMed and Google scholar. The papers and books were searched in Portuguese and English, using the following keywords: sexual orientation, sexual behavior, homosexuality, developmental Biology and genetics. Was selected papers of the last 22 years. Were found five main theories about the biological components: (1) fraternal birth order, (2) brain androgenization and 2D:4D ratio; (3) brain activation by pheromones; and (4) epigenetic inheritance; and four theories about the genetic components: (1) genetic polymorphism; (2) pattern of X-linked inheritance; (3) monozygotic twins; and (4) sexual antagonistic selection. Concluded that there were many scientific evidence found over time to explain some of biological and genetic components of homosexuality, especially in males. However, today, there is no definitive explanation about what are the determinants of homosexual orientation components

KIR gene content in amerindians indicates influence of demographic factors.

Although the KIR gene content polymorphism has been studied worldwide, only a few isolated or Amerindian populations have been analyzed. This extremely diverse gene family codifies receptors that are expressed mainly in NK cells and bind HLA class I molecules. KIR-HLA combinations have been associated to several diseases and population studies are important to comprehend their evolution and their role in immunity. Here we analyzed, by PCR-SSP (specific sequencing priming), 327 individuals from four isolated groups of two of the most important Brazilian Amerindian populations: Kaingang and Guarani. The pattern of KIR diversity among these and other ten Amerindian populations disclosed a wide range of variation for both KIR haplotypes and gene frequencies, indicating that demographic factors, such as bottleneck and founder effects, were the most important evolutionary factors in shaping the KIR polymorphism in these populations

Association of cytokines in individuals sensitive and insensitive to dust mites in a Brazilian population.

Allergic reaction to dust mites is a relatively common condition among children, triggering cutaneous and respiratory responses that have a great impact on the health of this population. Anaphylactic hypersensitivity is characterized by an exacerbated response involving the production of regulatory cytokines responsible for stimulating the production of IgE antibodies.To investigate an association of variants in cytokine genes (IL1A-889, IL1B-511, +3962, IL1R1970, IL1RA11100, IL4RA+1902, IL12-1188, IFNG+874, TGFB1 codon 10, codon 25, TNFA-308, -238, IL2-330, +166, IL4-1098, -590, -33, IL6-174, nt565, and IL10-1082, -819, -592) between patients sensitive to dust mites and a control group.A total of 254 patients were grouped as atopic and non-atopic according to sensitivity as evaluated by the Prick Test and to cytokine genotyping by the polymerase chain reaction-sequence specific primers (PCR-SSP) method using the Cytokine Genotyping Kit.A comparison between individuals allergic to Dermatophagoides farinae, Dermatophagoides pteronyssinus, and Blomia tropicalis and a non-atopic control group showed significant differences between allele and genotype frequencies in the regulatory regions of cytokine genes, with important evidence for IL4-590 in T/C (10.2% vs. 43.1%, odd ratio [OR] = 0.15, p = 5.2 10-8, pc = 0.0000011, and 95% confidence interval [95%CI] = 0.07-0.32) and T/T genotypes (42.9% vs. 13.8%, OR = 4.69, p = 2.5 10-6, pc = 0.000055, and 95%CI = 2.42-9.09). Other associations were observed in the pro-inflammatory cytokines IL1A-889 (T/T, C, and T) and IL2-330 (G/T and T/T) and the anti-inflammatory cytokines IL4RA+1902 (A and G), IL4-590 (T/C, T/T, C, and T), and IL10-592 (A/A, C/A, A, and C).Our results suggest a possible association between single nucleotide polymorphisms (SNPs) in cytokine genes and hypersensitivity to dust mites

Table1_Distribution of a novel CYP2C haplotype in Native American populations.DOCX

The CYP2C19 gene, located in the CYP2C cluster, encodes the major drug metabolism enzyme CYP2C19. This gene is highly polymorphic and no-function (CYP2C19*2 and CYP2C19*3), reduced function (CYP2C19*9) and increased function (CYP2C19*17) star alleles (haplotypes) are commonly used to predict CYP2C19 metabolic phenotypes. CYP2C19*17 and the genotype-predicted rapid (RM) and ultrarapid (UM) CYP2C19 metabolic phenotypes are absent or rare in several Native American populations. However, discordance between genotype-predicted and pharmacokinetically determined CYP2C19 phenotypes in Native American cohorts have been reported. Recently, a haplotype defined by rs2860840T and rs11188059G alleles in the CYP2C cluster has been shown to encode increased rate of metabolism of the CYP2C19 substrate escitalopram, to a similar extent as CYP2C19*17. We investigated the distribution of the CYP2C:TG haplotype and explored its potential impact on CYP2C19 metabolic activity in Native American populations. The study cohorts included individuals from the One Thousand Genomes Project AMR superpopulation (1 KG_AMR), the Human Genome Diversity Project (HGDP), and from indigenous populations living in Brazil (Kaingang and Guarani). The frequency range of the CYP2C:TG haplotype in the study cohorts, 0.469 to 0.598, is considerably higher than in all 1 KG superpopulations (range: 0.014—to 0.340). We suggest that the high frequency of the CYP2C:TG haplotype might contribute to the reported discordance between CYP2C19-predicted and pharmacokinetically verified CYP2C19 metabolic phenotypes in Native American cohorts. However, functional studies involving genotypic correlations with pharmacokinetic parameters are warranted to ascertain the importance of the CYP2C:TG haplotype.</p

Primers designed to solve discordant results obtained with previously described primer pairs.

a<p>modified from Gómez-Lozano & Vilches (2002) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056755#pone.0056755-GmezLozano2" target="_blank">[54]</a>;</p>b<p>modified from Uhrberg et al. (1997) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056755#pone.0056755-Uhrberg2" target="_blank">[55]</a>;</p>c<p>modified from Uhrberg et al. (2002) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056755#pone.0056755-Uhrberg1" target="_blank">[16]</a>;</p>d<p>modified from Du et al. (2007) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056755#pone.0056755-Du1" target="_blank">[56]</a>;</p>e<p>new.</p

Frequencies of haplogroups A and B estimated using two methods, in the Kaingang and Guarani populations.

<p>n = number of individuals; m1 = method 1– Bernstein’s formula, which assumes Hardy-Weinberg equilibrium; m2 = method 2– direct counting of the inferred A and B haplotypes.</p

Neighbor joining dendrogram of Nei’s genetic distances among populations, based on the KIR gene frequencies.

<p>Gene frequencies available on allelefrequencies.net <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056755#pone.0056755-GonzalezGalarza1" target="_blank">[24]</a>.</p

Haplotypes and their frequencies in the four Amerindian populations analyzed.

<p>Filled boxes indicate presence of the gene and blank boxes, absence. In dark blue are genes typically from haplotypes A and light blue, from haplotypes B.</p