A collaboration between more than 70 researchers across the globe has uncovered nine new genes on the X chromosome that, when knocked-out, lead to learning disabilities. The international team studied almost all X chromosome genes in 208 families with learning disabilities - the largest screen of this type ever reported. Learning Disabilities In Males: Nine New X Chromosome Genes Linked To Learning Disabilities
Remarkably, the team also found that approximately 1-2% of X chromosome genes, when knocked-out, have no apparent effect on an individual's ability to function in the ordinary world. The publication in Nature Genetics - a culmination of five years of scientific collaboration - emphasises the power of sequencing approaches to identify novel genes of clinical importance, but also highlights the challenges researchers face when carrying out this kind of study.
Estimates suggest that the prevalence of learning disability is 2-3%. Learning disability is significantly more common in males than in females and genetic causes have long been sought on the X chromosome: males have only one X chromosome and so a gene mutation on the X is more likely to have an effect in males than in females.
"We sequenced 720 out of the approximately 800 known genes on the X chromosome in more than 200 families affected by X-linked learning disabilities," explains Professor Mike Stratton, from the Wellcome Trust Sanger Institute. "This is the largest sequencing study of complex disease ever reported."
In part because of their apparent effects in males, X-linked disorders have been well studied by geneticists over the past 25 years. Conceived by Dr Lucy Raymond, from the University of Cambridge, and Professor Mike Stratton, the collaborative study harnessed DNA sequencing to detect as many new abnormal genes as possible. In the future similar strategy will be used to find disease causing sequence variants implicated in other complex genetic diseases.
Some characteristics in common could be identified in patients with variants in the same gene. However, in many, learning disability was the only feature. The newly identified genes play roles in a wide range of biological processes suggesting that disruption to many cellular machines can damage the nervous system.
"As well as these important new gene discoveries relating to learning disability, we have also uncovered a small proportion - 1% or more - of X chromosome protein-coding genes that, when knocked out, appear to have no effect on the characteristics of the individual," explains Mike Stratton. "It is remarkable that so many protein-coding genes can be lost without any apparent effect on an individual's normal existence - this is a surprising result and further research will be necessary in this area."
This finding will also act as a warning to geneticists. Large-scale studies are designed to uncover associations between knocked-out genes and disease. However, this study shows that a small proportion of gene knock-outs have no discernible effect on the individual. In future studies, researchers must therefore be cautious about assuming that the presence of a knocked out gene in an individual with a particular disease means that the knocked out gene is causing the disease.
The research comes towards the end of a long process of gene cataloguing in this field. Scientists believe that there are likely to be more undiscovered genes that contribute to X-linked learning disabilities; however, variants at what are expected to be lower frequency will become increasingly difficult and costly to uncover. The next challenge is to implement this improved knowledge of the complex of genes that lead to learning disabilities in clinical practice.
"We already offer genetic counselling to families with X-linked learning disabilities," says Dr Lucy Raymond, Reader in Neurogenetics, Cambridge Institute for Medical Research at the University of Cambridge. "This new research uncovers yet more genes that can be incorporated to improve the provision of diagnostics to families with learning disabilities and allow us to develop more comprehensive genetic counselling in the future, allowing parents and the extended family to make the most informed family planning decisions."
Although in most cases improved treatments remain to be developed, information about a genetic condition can provide support to affected families. The information can also help to inform reproductive choices.
This research was supported by the New South Wales Department of Health, the Australian National Health and Medical Research Council, the SMILE foundation, the WCH Foundation, Adelaide, Mr D Harwood, the European Union, the US National Institutes of Health, the South Carolina Department of Disabilities and Special Needs (SCDDSN), Action Medical Research and the Wellcome Trust.
* * * Journal reference: 1.Tarpey PS et a. A systematic, large-scale resequencing screen of the X chromosome coding exons in mental retardation. Nature Genetics, DOI: 10.1038/ng.367
“You wait till Larry comes and I tell him my theory!” The bids, duly sealed, were given into the keeping of the commissary officer to be put in his safe, and kept until the day of judgment, when all being opened in public and in the presence of the aspirants, the lowest would[Pg 188] get the contract. It was a simple plan, and gave no more opportunity for underhand work than could be avoided. But there were opportunities for all that. It was barely possible—the thing had been done—for a commissary clerk or sergeant, desirous of adding to his pittance of pay, or of favoring a friend among the bidders, to tamper with the bids. By the same token there was no real reason why the commissary officer could not do it himself. Landor had never heard, or known, of such a case, but undoubtedly the way was there. It was a question of having the will and the possession of the safe keys. "Well, I believe our boys 's all right. They're green, and they're friskier than colts in a clover field, but they're all good stuff, and I believe we kin stand off any ordinary gang o' guerrillas. I'll chance it, anyhow. This's a mighty valuable train to risk, but it ought to go through, for we don't know how badly they may need it. You tell your engineer to go ahead carefully and give two long whistles if he sees anything dangerous." "Fine-looking lot of youngsters," he remarked. "They'll make good soldiers." "That's just what he was, the little runt, and we had the devil's own time finding him. What in Sam Hill did the Captain take him for, I'd like to know? Co. Q aint no nursery. Well, the bugler up at Brigade Headquarters blowed some sort of a call, and Skidmore wanted to know what it meant. They told him that it was an order for the youngest man in each company to come up there and get some milk for his coffee tomorrow morning, and butter for his bread. 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They asked why we didn't get the right kind of nurses for our company, that wouldn't let the members stray out of their sight? Why we didn't call the children in when the chickens went to roost, undress 'em, and tuck 'em in their little beds, and sing to 'em after they'd said 'Now I lay me down to sleep?' I stood it all until that big, hulking Pete Nasmith came down with a camp-kettle, which he was making ring like a bell, as he yelled out, 'Child lost! Child lost!' Behind him was Tub Rawlings singing, 'Empty's the cradle, baby's gone.' Then I pulled off my blouse and slung it into my tent, and told 'em there went my chevrons, and I was simply Scott Ralston, and able to lick any man in Co. A. One o' their Lieutenants came out and ordered them back to their quarters, and I deployed the company in a skirmish-line, and started 'em through the brush toward Brigade Headquarters. About three-quarters o' the way Osc Brewster and Ol Perry, when going through a thicket, heard a boy boo-hooing. They made their way to him, and there was little Skidmore sitting on a stump, completely confused and fagged out. He'd lost his way, and the more he tried to find it the worse he got turned around. They called out to him, and he blubbered out: 'Yes, it's me; little Pete Skidmore. Them doddurned fools in my company 've lost me, just as I've bin tellin' 'em right along they would, durn 'em.' Osc and Ol were so tickled at finding him that they gathered him up, and come whooping back to camp, carrying him every step of the way." And the rush stopped. Cadnan waited for a second, but there was no more. "Dara is not to die," he said. Then he saw Orion hanging over him, very low in the windy sky, shaking with frost. His eyes fixed themselves on the constellation, then gradually he became aware of the sides of a cart, of the smell of straw, of the movement of other bodies that sighed and stirred beside him. The physical experience was now complete, and soon the emotional had shaped itself. Memory came, rather sick. He remembered the fight, his terror, the flaming straw, the crowd that constricted and crushed him like a snake. His rage and hate rekindled, but this time without focus—he hated just everyone and everything. He hated the wheels which jolted him, his body because it was bruised, the other bodies round him, the stars that danced above him, those unknown footsteps that tramped beside him on the road. Farewell to Jane and Caroline!" HoME大香蕉色人阁 ENTER NUMBET 0017
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Transhumanism: Brave New World?
Critique of Aldous Huxley's Brave New World
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