The common autoimmune disease type 1 diabetes provides a paradigm for the genetic analysis of multifactorial disease. Disease occurrence is attributable to the interaction with the environment of alleles at many loci interspersed throughout the genome. Their mapping and identification is difficult because the disease-associated alleles occur almost as commonly in patients as in healthy individuals; even the highest-risk genotypes bestow only modest risks of disease. The identification of common quantitative trait loci (QTL) in autoimmune disease and in other common (...) disorders, therefore,requires a very close marriage of genetics and biology. Two QTLs have been identified in human type 1 diabetes: the major histocompatibility complex HLA class II loci and a promoter polymorphism of the insulin gene. The evidence for their primary roles in disease aetiology demonstrates the necessity of combined studies of genetics and biology. Their functions and interaction underpin an emerging picture of the basic causes of the disease and direct analyses towards other candidate genes and pathways. The genetic tools used for QTL identification include transgenesis and gene knockouts, whole genome scanning for linkage, mouse congenic strains, linkage disequilibrium mapping, and the establishment of ancestral haplotypes among disease-associated chromosomes. BioEssays 1999;21:164–174. © 1999 John Wiley & Sons, Inc. (shrink)

This historic book may have numerous typos and missing text. Purchasers can usually download a free scanned copy of the original book (without typos) from the publisher. Not indexed. Not illustrated. 1799 edition. Excerpt:... chapter viii. discipline' of the heart. One of the first steps to be taken, if you would have a character that will stand by you in prosperity and in adversity, in life and death, is to fortify your mind, with fixed principles. There is no period of (...) life in which the heart is so much inclined to scepticism and infidelity as in youth. Not that young men are infidels, but the mind is tossed from doubt to doubt, like a light boat leaping from wave to wave. There is no positive settling down into deism or infidelity, but the heart is full of doubting, so that the mind has no position, in morals or religion, fortified. If the restraints of education are so far thrown off as to allow you to indulge in sin, Which is in any way disgraceful if known, you will then easily become an infidel. "The nurse of infidelity is sensuality. The young are sensual. The Bible stands in their way. It prohibits the indulgence of ' the lust of the flesh, the lust of the eye, and the pride of life.' But the young mind loves these things, and therefore it hates the Bible, which prohibits them. It is prepared to say, ' If any man will bring me arguments against the Bible, I will thank him; if not, I will invent them.' As to infidel arguments, there is no weight in them. They are jejune and refuted. Infidela are not themselves convinced by them. What sort of men are infidels? They are loose, fierce, overbearing men. There is nothing in them like sober and serious inquiry. They are the wildest fanatics on earth. Nor have they agreed among themselves on any scheme of truth and felicity. Look at the needs and necessities of man. 'Every pang of grief tells a man he needs a helper; but infidelity provides none. And what can its schemes do for you in death?' Examine your... (shrink)

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