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【Nature】Getting personal

Getting personal
The possibility of more widespread application of ‘personalized medicine’, in which therapy is tailored to factors such as an individual’s genetic make-up, has been on the horizon for years, but so far, translation of this concept to clinical practice has been limited. What might it take to change this situation?
This year marks the 150th anniversary of the birth of the British doctor Archibald Garrod, who coined the term ‘inborn error of metabolism’ to refer to monogenic diseases such as alkaptonuria — a disorder characterized by symptoms such as pigmented urine that is now known to be caused by the inheritance of two abnormal copies of the gene that encodes homogentisic acid oxidase. Garrod has also been credited with making the first proposal of a familial component in the variability of the effects of drugs, which might be considered to be the birth of the field of pharmacogenetics
今年是英国医生Archibald Garrod的150周年诞辰,Garrod首先用“先天性代谢缺陷”来指代单基因遗传的疾病如黑尿病等,这种疾病的症状是出现色素尿,目前已知是被编码尿黑酸氧化酶基因的两个异常的拷贝所造成的。Garrod首先提出家族性组成的遗传变异影响药物的作用,这可以被视为药理遗传学领域的诞生。
Now, several decades on from these ground-breaking proposals, it seems that the understanding of the genetic basis of diseases and of the responses to drugs is entering a new era. For example, as discussed in a news feature on page 590 of this issue, the past year has seen a flurry of genome-wide association studies that have identified genetic variants linked with various common complex diseases such as type 2 diabetes, rheumatoid arthritis and prostate cancer. Elucidating the genetic factors underlying such diseases poses a much greater challenge than that for monogenic diseases such as alkaptonuria, as these diseases are related to the complex interaction of multiple genes — each typically with a small effect — and environmental factors. Such challenges, however, are increasingly now being successfully tackled.
The completion of the sequencing of the human genome at the start of this decade has been a key to this
success, but it is only recently that several other advances have begun to allow more of the potential of this genomic knowledge to be realized. In the case of genome-wide association studies, important information has also come from the cataloguing of genomic variations in the form of single nucleotide polymorphisms and data on their statistical relatedness from the HapMap project (http://www.hapmap.org). Coupling the availability of such information with increasingly powerful highthroughput technologies for genotyping has made the analysis of the potential linkage of up to 500,000 genetic variants with disease in thousands of subjects practically and financially feasible. As a result, a wide variety of clues — both expected and unexpected — about the genetic basis of disease are being revealed.

As such knowledge is likely to grow rapidly with the completion of further genome-wide association
studies, also including those studying variations in drug response, a key question as always is how the knowledge might be translated into therapeutic applications. This question was the basis for a recent symposium entitled Personalized medicine: prospect or pipedream? organized by the Institute for Translational Medicine and Therapeutics (http://www.itmat.upenn.edu) in Philadelphia, USA, and supported by Nature Reviews Drug Discovery.


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作者:admin@医学,生命科学    2011-08-23 17:36