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Autor     Michael Nothnagel
Titel    The Definition of Multilocus Haplotype Blocks and Common Diseases
Herausgeber    Arbeitsgruppe Bioinformatik des Max-Delbrück-Centrums für Molekulare Medizin (MDC), Berlin-Buch, in Kooperation mit der Medizinischen Fakultät der Charité - Universitätsmedizin Berlin
Ort    Berlin
Datum    6. Januar 2005
Anmerkung    Dissertation zur Erlangung des akademischen Grades Doctor rerum medicarum (Dr. rer. medic.) im Fach Medizin vorgelegt der Medizinischen Fakultät der Charité – Universitätsmedizin Berlin Humboldt-Universität zu Berlin. Eingereicht am 03. März 2004, Tag der mündlichen Prüfung: 13. Dezember 2004.
URL    http://edoc.mdc-berlin.de/8593/, http://edoc.hu-berlin.de/dissertationen/nothnagel-michael-2004-12-13/PDF/Nothnagel.pdf

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Zuletzt bearbeitet: 2016-05-06 14:32:26 Graf Isolan
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Seite: 1, Zeilen: 1-17
Quelle: Nothnagel 2005
Seite(n): 1, Zeilen: 2-3, 7-20
1 Introduction

1.1 Genetic background of diseases

Diseases with a genetic component, like other phenotypic traits, are usually distinguished as being either Mendelian or complex. Mendelian traits are characterized by well-defined phenotypes, one or two genetic disease loci with high penetrance, a small phenocopy rate and usually small susceptibility allele frequencies. This clear genotype-phenotype relation results in a clear pattern of inheritance. Mendelian diseases are usually rare in the population. Complex traits show a less clear relationship between genotype and phenotype due to two or more of the following characteristics: ill-defined phenotypes, incomplete penetrance, high phenocopy rate, genetic heterogeneity, oligogenic or polygenic inheritance, epistasis, mitochondrial inheritance, imprinting, and an often large contribution of environmental influences (Lander and Schork, 1994; Belmont and Leal, 2005; Gulcher and Stefansson, 2006).

Unfortunately, almost all common, non-infectious diseases have a genetic component and fall into the category of complex traits. Examples are heart disease, cancer, arthritis, asthma, diabetes, hypertension, lipid metabolism disorders, some forms of Alzheimer’s disease, and depression.


Belmont, J. W. & Leal, S. M. (2005) Complex phenotypes and complex genetics: an introduction to genetic studies of complex traits. Curr Atheroscler Rep, 7(3): 180–187.

Gulcher, J. & Stefansson, K. (2006) Positional cloning: complex cardiovascular traits. Methods Mol Med, 128: 137–152.

Lander, E. S. & Schork, N. J. (1994) Genetic dissection of complex traits. Science, 265(5181): 2037–2048.

Chapter 1

Introduction

1.1 Genetic background of diseases

[...] Diseases with a genetic component, like other phenotypic traits, are usually distinguished as being either Mendelian or complex. Mendelian traits are characterized by well-defined phenotypes, one or two genetic disease loci with high penetrance, a small phenocopy rate and usually small susceptibility allele frequencies. This clear genotype-phenotype relation results in a clear pattern of inheritance. Mendelian diseases are usually rare in the population.

Complex traits show a less clear relationship between genotype and phenotype due to two or more of the following characteristics: ill-defined phenotypes, incomplete penetrance, high phenocopy rate, genetic heterogeneity, oligogenic or polygenic inheritance, epistasis, mitochondrial inheritance, imprinting, and an often large contribution of environmental influences [85].

Unfortunately, most common diseases in humans resemble complex traits. Examples are hypertension, lipid metabolism disorders, some forms of Alzheimer’s disease, and depression.


[85] E. S. Lander and N. J. Schork. Genetic dissection of complex traits. Science, 265(5181): 2037–48, Sep 30 1994.

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