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Post by Admin on Dec 17, 2018 18:16:46 GMT
It's generally understood that the biological sex of an embryo is determined by the chromosomes at conception – two X chromosomes will develop as female, while an XY combo will become male. But this simple rule may be too simple. The Y chromosome dictates male development through certain genes: it carries a gene called SRY, which in turn ramps up activity on another gene known as SOX9. High levels of SOX9 triggers development of testes in an embryo, creating a biological boy. The researchers set out to check how the SOX9 gene was regulated by segments of DNA known as enhancers, and how disruptions to these enhancers could lead to DSD conditions. "We discovered three enhancers that, together ensure the SOX9 gene is turned on to a high level in an XY embryo, leading to normal testis and male development," says Andrew Sinclair, lead author of the study. "Importantly, we identified XX patients who would normally have ovaries and be female but carried extra copies of these enhancers (high levels of SOX9), and instead developed testes. In addition, we found XY patients who had lost these SOX9 enhancers, (low levels of SOX9) and developed ovaries instead of testes." Fig. 1 These enhancers were found among what has in the past been referred to as "junk DNA." Although this makes up about 90 percent of human DNA, it has historically been overlooked because it doesn't contain genes. But that doesn't mean it's useless, as studies like this highlight. With about a million enhancers regulating the activity of about 22,000 genes, clues to new treatments could be hiding in this so-called junk DNA. A human SOX9 enhancer associated with 46,XX and 46XY DSD We focused on genetic intervals in the 2 Mb SOX9 upstream regulatory region that were previously associated with 46,XY and 46,XX DSD16,17,18,19,20,21,22. First, we analysed a 32.5 kb region, known as XYSR (17q24.3), ~500 kb upstream of SOX9 and TESCO, deletion of which causes 46,XY sex reversal17 (Fig. 1a). From a cohort of 44 DSD patients we identified two further duplications mapping to 17q24.3 in two unrelated 46,XX DSD patients lacking SRY. Patient 1 (46,XX testicular DSD) carries a 23.9 kb duplication, while Patient 2 (46,XX ovotesticular DSD) carries a 24.2 kb duplication (Fig. 1b and Supplementary Figure 1). CGH-array showed these duplications overlapped with each other and the XYSR region, defining a minimum critical region of 5.2 kb (Fig. 1b). Therefore, we anticipated that this redefined region would include a core gonadal enhancer for SOX9 implicated in both 46,XY and 46,XX DSD (Fig. 1b). In this study, we have identified human enhancers that contribute to SOX9 expression, and in which genetic aberrations lead to sex reversal. The first two enhancers, eSR-A and eSR-B, were located using new patient CNV data. Both of these enhancers show activation by SOX9 alone or in combination with SF1, but little activation by SRY, the initiator of testis differentiation. eSR-A and eSR-B must logically be active in the absence of SRY in vivo, because their duplication results in SOX9 overexpression in XX patients without SRY, ultimately causing XX sex reversal. Nature Communicationsvolume 9, Article number: 5319 (2018)
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Post by Admin on Dec 24, 2018 19:38:53 GMT
A particular region on chromosome 15 plays a major role in eye color. Within this region, there are two genes located very close together: OCA2 and HERC2. The protein produced from the OCA2 gene, known as the P protein, is involved in the maturation of melanosomes, which are cellular structures that produce and store melanin. The P protein therefore plays a crucial role in the amount and quality of melanin that is present in the iris. Two pigmentation genes called OCA2 and HERC2 on chromosome 15 are primarily responsible for human eye colors. Most East Asians only have the OCA2 gene and they naturally have brown eyes, while the frequency of HERC2 in East Asia is less than 2%. The HERC2 gene acts as a promoter of the OCA2 gene to trigger a change from brown to blue eyes. The frequencies of the HERC2 gene are more than 90% in northern Europe and less than 50% in southern Europe. Allele frequencies of rs12913832 in human populations surveyed as part of the Human Genome Diversity Project. The SNP, rs12913832, is in the HERC2 gene. A region of the nearby HERC2 gene known as intron 86 contains a segment of DNA that controls the activity (expression) of the OCA2 gene, turning it on or off as needed. At least one polymorphism in this area of the HERC2 gene has been shown to reduce the expression of OCA2, which leads to less melanin in the iris and lighter-colored eyes. Several other genes play smaller roles in determining eye color. Some of these genes are also involved in skin and hair coloring. Genes with reported roles in eye color include ASIP, IRF4, SLC24A4, SLC24A5, SLC45A2, TPCN2, TYR, and TYRP1. The effects of these genes likely combine with those of OCA2 and HERC2 to produce a continuum of eye colors in different people. Genetics of Pigmentation Diversity
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Post by Admin on Dec 27, 2018 18:21:51 GMT
A team of researchers at the University of Gothenburg has found that when infants live with pets, they grow up to have fewer allergies and other diseases. In their paper published on the open access site PLOS ONE, the group describes their study of datasets that held information on children's health and whether they had lived with pets as infants, and what they found. It is commonly believed that allowing infants and children to come into contact with germs helps their immune system to grow stronger, offering them more protection later in life. In this new effort, the team in Sweden sought to learn more about the possible benefits of germ exposure to infants living with pets in their home. Fig 1. Data from the cross-sectional study. The study by the team consisted of analyzing data from databases built around two previous studies that involved tracking childrens' health and which also held information about pets in their homes. One of the datasets included information for 1,029 children that were either seven or eight years old. In that dataset, the researchers found that the incidence of allergies (which in this study included asthma, eczema, hay fever and allergic rhinoconjunctivitis) was 49 percent for children who had not been exposed to pets as infants. That number fell to 43 percent for children who had lived with a single pet as an infant and to 24 percent for children who had lived with three pets. Fig 2. Data from the Birth Cohort. The second dataset held information on 249 children— it showed that the allergy rate for children growing up without a pet was 48 percent, 35 percent for children with one pet and just 21 percent for children who had grown up with multiple pets. The researchers suggest that taken together, the two datasets show that the more exposure infants have to pets, they less likely they are to develop allergies later in life. They also note that having pets is just one way to reduce allergy risk, other factors such as being born vaginally, living on a farm and having more siblings have also been shown to reduce the risk—as has parents sucking on a baby's pacifier before handing it to them. More information: Bill Hesselmar et al. Pet-keeping in early life reduces the risk of allergy in a dose-dependent fashion, PLOS ONE (2018).
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Post by Admin on Jan 6, 2019 18:11:29 GMT
Blonds are more complex than anyone realised. Scientists have unravelled the mystery of hair colour, finding that blond hair needs 200 genes to create it, compared with 60 for brown locks and a handful for most redheads. The finding emerged from studying the DNA of 39,397 blond men and women — probably the biggest blond sample science has considered. Their genes were compared with those of 15,731 redheads — also a record — and 283,930 people with brown or black hair. “Blond hair is associated with over 200 genetic variants,” said the researchers, led by the Medical Research Council’s human genetics unit at Edinburgh University. This may explain why true blonds are rare. Such hair is found on only 9.9% of men and 12.7% of women. The derived allele of the KITLG SNP rs12821256 that is associated with – and likely causal for – blond hair in Europeans [4,5] is present in one hunter-gatherer from each of Samara, Motala and Ukraine (I0124, I0014 and I1763), as well as several later individuals with Steppe ancestry. Since the allele is found in populations with EHG but not WHG ancestry, it suggests that its origin is in the Ancient North Eurasian (ANE) population. Consistent with this, we observe that earliest known individual with the derived allele is the [Siberian] ANE individual Afontova Gora 3 which is directly dated to 16130-15749 cal BCE (14710±60 BP, MAMS-27186:Mathieson et al. 2017.)
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Post by Admin on Feb 23, 2019 17:29:29 GMT
In remote Southeastern Siberia in the large Denisova Cave, archaeologists have found evidence of multiple human ancestors, including bones of Neanderthals and artifacts of early modern human culture. But there was also evidence that yet another species, known only as Denisovans, also occupied the cave. The Denisovans are the least-known and most mysterious of our ancestors. DNA extracted from a finger bone provided ironclad evidence that Denisovans were distinct from Neanderthals. The evidence of Denisovans is very limited. Correspondent Ann Gibbons writes in Science that the only remains are a child’s finger bone and a couple of teeth. DNA extracted from the finger bone provided ironclad evidence that Denisovans were distinct from Neanderthals. Unfortunately, researchers have learned little about the Denisovans, except that the finger bone belonged to a young girl. The teeth, both molars, were similarly unhelpful. Analysis showed that the large teeth were distinct from both Neanderthal and human teeth. While it has been difficult to learn about the Denisovans directly, nevertheless the genetic evidence is so clear that it has been possible to search for markers in the modern human genome. It has long been known that Neanderthals and Modern Humans frequently interbred, and apparently the Denisovans got in the mix too. The interchange appears to have been beneficial, exchanging genes that helped shape our immune system. Aboriginal Australians share up to 5% of Denisovan DNA, suggesting that the species once roamed far beyond the Altai Mountains and probably across East Asia. At some point they must have interbred with the Melanesian people who set sail and populated Australia tens of thousands of years ago. The extent to which the species overlapped within Denisova Cave has long been a subject of speculation, but Elizabeth Pennisi writes that there was extensive interbreeding between Neanderthals and Denisovans. Pennisi also describes how Denisovan remains contain evidence of yet another, even more ancient species that is still unknown with which they must have interbred in the distant past. It seems Denisova Cave could be the setting for an ancient soap opera. New research helps explain how this happened: additional discoveries suggest that Denisovans and Neanderthals may have overlapped in the cave for up to 50,000 years.
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