Variation in the Human Genome and the Inherited Basis of Common Disease

doi:10.1053/j.seminoncol.2006.11.001

Seminars in Oncology

Volume 33, Supplement 11, December 2006, Pages 46-49

https://doi.org/10.1053/j.seminoncol.2006.11.001 Get rights and content

The availability of a reference human genome sequence–an increasingly dense catalog–knowledge of common genetic variation, and new developments in technology present an unprecedented opportunity to systematically explore the genetic basis of complex human diseases such as cancer. An understanding of the common mutations that can cause distinct human cancers will be critical for identifying new targets for drug discovery, patient stratification for clinical trials, and analysis of drug response data to delineate classes of patients that respond to therapy. The genome structure of cancer can be investigated in several ways. Germline mutations can be investigated in large-scale, case-control, or family studies. Somatic alternations can be identified using state-of-the-art genomic technologies such as high-density oligonucleotide arrays and targeted resequencing. Combined, these approaches will lead to a better understanding of the cancer genome.

Section snippets

Examples of the Utility of Haplotype-Based Studies

Two recent examples of haplotype-based studies illustrate the power of the approach and the dramatic effect the identification of risk alleles for common disease could have on human heath. The first is the discovery of a common allele which explains a substantial portion of risk for the debilitating blindness disease, AMD. Only a subset of published linkage studies of AMD displayed modest positive LOD scores across a region of chromosome 1.²⁵ However, whole-genome association analysis¹⁶ and

Considerations for Cancer

The use of genetics and genomics technologies offers great promise for cancer research. Cancer presents a particular challenge, compared with the genetic studies discussed earlier, because each human cancer is composed of two genomes: the germline and the somatic genome. Tools to discover heritable germline variants for cancer risk are the same as discussed above for other common, complex diseases, and should be greatly enabled in the coming year through use of HapMap and the application of

Conclusion

In summary, the fruits of the complete human genome sequence and the HapMap project coupled with technologic advances offer unprecedented opportunities to completely characterize the somatic cancer genome and the risk contributed by common variations in the germline to cancer risk.

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Genetic variations can occur as DNA sequence repeats, insertions or deletions [88]. The most commonly occurring gene variants are single nucleotide polymorphisms (SNPs) and these have developed within humans over time passing down through generations [88,89]. SNPs are considered relevant when detected in greater than 1% of the population [88,90].
Dry eye disease (DED) is a complex condition with a multifactorial etiology that can be difficult to manage successfully. While external factors are modifiable, treatment success is limited if genetic factors contribute to the disease. The purpose of this review is to compile research describing normal and abnormal ocular surface function on a molecular level, appraise genetic studies involving DED or DED-associated diseases, and introduce the basic methods used for conducting genetic epidemiology studies.
Distributions of Sasang constitutions and six syndromes in patients with functional dyspepsia and healthy subjects
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To investigated the characteristics of patients with functional dyspepsia (FD) in terms of Sasang constitutional medicine.
A total of 116 patients with FD were recruited based on diagnosis by gastroscopy and symptomatic measurements. The distributions of Sasang constitutions and six syndromes in terms of TKM theory in the patients was compared with those from 1423 healthy subjects.
The distribution of Sasang constitutions for the patients with FD significantly differed from that for healthy subjects, especially among women; 36.7% vs 45.6% for Taeumin, 28.9% vs 33.9% for Soumin, and 34.4% vs 20.4% for Soyangin. Our results assumed a high prevalence in Soyangin women (around 1.7 folds), and Soumin (45.2%), in particular, had a high prevalence of “deficiency and coldness of spleen and stomach” compared with Taeumin (14.9%) and Soyangin types (15.7%).
This study identified a trend for the frequency of FD and the Sasang constitutions. The findings may provide new ideas for the study of prevention and management of FD.
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Sasang constitutional medicine is a component of Traditional Korean Medicine that stresses the hereditary makeup of disease incidences or therapeutic responses. This study investigated the relationship between the incidence of cancer and Sasang constitution classification.
Five hundred and one cancer patients were classified as having one of the four types of Sasang constitutions (Taeumin, Soumin, Soyangin, Taeyangin) using Questionnaire for Sasang Constitution Classification II, then compared with data from 1423 healthy subjects.
The Sasang constitutional distribution for the cancer patients was significantly different from that for healthy subjects: 22.8% vs 46.9% for Taeumin, 35.5% vs 24.0% for Soumin, and 41.7% vs 29.1% for Soyangin. Our results assumed that the lowest cancer incidence would be in Taeumin (around 2-fold in both sex) while the highest cancer incidence in Soumin males (2.8-fold) and Soyangin females (2.1-fold).
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Sasang constitution affects the prevalence of functional dyspepsia
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Serum Levels of Stress Hormones and Oxidative Stress Biomarkers Differ according to Sasang Constitutional Type
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Are race-specific ERCC1 haplotypes in melanoma cases versus controls related to the predictive and prognostic value of ERCC1 N118N?
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Variation in the Human Genome and the Inherited Basis of Common Disease

Section snippets

Examples of the Utility of Haplotype-Based Studies

Considerations for Cancer

Conclusion

Cell

Genet Med

Am J Hum Genet

Am J Hum Genet

Am J Hum Genet

Linkage of early-onset familial breast cancer to chromosome 17q21

Science

Identification of the breast cancer susceptibility gene BRCA2

Nature

The future of genetic studies of complex human diseases

Science

SinProstate cancer susceptibility genes: Lessons learned and challenges posed

Endocr Relat Cancer

Variation is the spice of life

Nat Genet

Quality and completeness of SNP databases

Nat Genet

Apolipoprotein E and Alzheimer disease

Proc Natl Acad Sci U S A

Resistance to activated protein C caused by the factor VR506Q mutation is a common risk factor for venous thrombosis

Thromb Haemost

The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes

Nat Genet

The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetesBelgian Diabetes Registry

Hum Mol Genet