From Genotype to Phenotype

by Malcolm

• ISBN13: 9780124662575
• ISBN10: 0124662579
• Edition: 1st
• Format: Hardcover
• Copyright: 2001-11-19
• Publisher: Elsevier Science

Summary

This volume of the Human Molecular Genetics series covers such genotype-phenotype correlations as clinical and environmental aspects, gene structure, expression, and mutation. Also discussed are models of certain diseases and future prospects for treatment and prevention. This book provides the reader with a basic overview of the physical expression of genetic disease before discussing in detail the most recent research and therapeutic developments.

Table of Contents

Contributors	ix
Abbreviations	xi
Preface	xv
Genotype to phenotype: interpretations of the human genome project	1	(12)
Sue Malcolm
The genome project	1	(3)
Mutation vs. polymorphism	4	(2)
The mutation defines the disorder	6	(1)
Interacting genes	7	(3)
Conclusions	10	(3)
From protein sequence to structure and function	13	(18)
Sylvia B. Nagl
Introduction	13	(1)
Predicting gene function	14	(12)
Future directions: toward a `global biology'	26	(5)
Genes in population	31	(24)
Francois Cambien
Population structure and dynamics	31	(1)
Genetic variability and evolution	32	(18)
Conclusion	50	(5)
Gene-environment interaction: lipoprotein lipase and smoking and risk of CAD and the ACE and exercise-induced left ventricular hypertrophy as examples	55	(18)
Steve E. Humphries
Philippa J. Talmud
Hugh Montgomery
Introduction	55	(1)
Risk factors for CAD	56	(2)
Homeostasis and use of stressing the genotype to identify functional variants	58	(2)
How mutations identify rate-limiting steps in biochemical pathways	60	(8)
Analytical problems for gene-environment interaction studies	68	(1)
Conclusions	68	(5)
Pharmacogenomics	73	(12)
Ann K. Daly
Introduction	73	(1)
Genetic polymorphisms relating to drug metabolism and disposition	73	(7)
Polymorphisms affecting drug targets	80	(2)
The future for pharmacogenomics	82	(3)
Mitochondrial genetics	85	(22)
P.F. Chinnery
D.M. Turnbull
Introduction	85	(1)
Basic mitochondrial genetics and biochemistry	85	(2)
Polymorphic variability of the mitochondrial genome	87	(1)
Pathogenic mitochondrial DNA defects and disease	88	(4)
From genotype to biochemical phenotype	92	(1)
From genotype to clinical phenotype	93	(3)
The inheritance of pathogenic mtDNA defects	96	(2)
The investigation of patients with suspected mtDNA disease	98	(2)
Therapeutic manipulation of the mitochondrial genome	100	(1)
Conclusion	101	(6)
Identification of disease susceptibility genes (modifier) in mouse models: cancer and infectious disease	107	(24)
Tom van Wezel
Marie Lipoldova
Peter Demant
Introduction	107	(4)
Cancer genetics in mouse strains, current QTLs	111	(8)
Use of RCS for analysis of immune response	119	(5)
Summary	124	(7)
The GNAS1 gene	131	(16)
D.T. Bonthron
Introduction	131	(1)
Pseudohypoparathyroidism (PHP) and Albright hereditary osteodystrophy (AHO)	131	(4)
Anomalous inheritance of PHP-la - imprinting of GNAS1	135	(4)
Mutational spectrum of GNAS1	139	(1)
Activating mutations of GNAS1	140	(1)
PHP-lb; a tissue-specific GNAS1 imprinting defect	141	(1)
Mechanistic heterogeneity in PHP-lb	142	(1)
Summary	142	(5)
Genomic disorders	147	(18)
Susan L. Christian
David H. Ledbetter
Introduction	147	(1)
Type I: single gene disorders	147	(5)
Type II: contiguous gene syndromes	152	(5)
Mechanism of rearrangement	157	(3)
Conclusions	160	(5)
Genotype to phenotype in the spinocerebellar ataxias	165	(24)
Paul F. Worth
Nicholas W. Wood
Introduction	165	(2)
Molecular characteristics of CAG repeats	167	(6)
Genotype-phenotype correlation	173	(3)
Clinico-pathological correlation	176	(2)
Pathophysiology of trinucleotide repeat disorders	178	(3)
Conclusions	181	(8)
Disorders of cholesterol biosynthesis	189	(20)
David R. Fitzpatrick
Introduction	189	(1)
The function of membrane cholesterol	189	(1)
Related sterols	189	(1)
The origins of cellular cholesterol	190	(1)
Endogenous synthesis of cholesterol	190	(4)
Inborn errors of cholesterol biosynthesis	194	(1)
Mevalonate kinase deficiency	194	(2)
3-sterol dehydrogenase (3SD) deficiency	196	(2)
Sterol isomerase deficiency	198	(1)
7-dehydrocholesterol reductase deficiency	199	(2)
24 sterol reductase deficiency	201	(1)
The mechanism of developmental pathology	202	(1)
Future research	203	(6)
Mutations in the human HOX genes	209	(20)
Frances R. Goodman
Introduction	209	(2)
Synpolydactyly (SPD) and HOXD13	211	(3)
Hand-foot-genital syndrome (HFGS) and HOXA13	214	(3)
Hemizygosity for the HOXA and HOXD gene clusters	217	(1)
Functional effects of the HOXD13 and HOXA13 mutations	218	(4)
What further HOX gene mutations remain to be found	222	(7)
PITX2 gene in development	229	(10)
J. Murray
E. Semina
Introduction	229	(1)
Roles of PITX2 in development	229	(6)
The Pitx family	235	(1)
Conclusion	235	(4)
The hedgehog pathway and developmental disorders	239	(14)
Allan E. Bale
Introduction	239	(1)
Biochemistry of the hedgehog pathway	240	(2)
What human disease and mouse models tell us about the function of the hedgehog pathway	242	(6)
Conclusions	248	(5)
X-linked immunodeficiences	253	(22)
H. B. Gaspar
Christine Kinnon
Introduction	253	(1)
X-linked severe combined immunodeficiency	253	(5)
X-linked agammaglobulinemia (XLA)	258	(4)
Wiskott-Aldrich syndrome	262	(2)
X-linked lymphoproliferative syndrome	264	(2)
X-linked chronic granlomatous disease	266	(1)
X-linked hyper IgM syndrome	267	(1)
Properdin deficiency	268	(7)
The ubiquitin-proteasome system and genetic diseases: protein degradation gone awry	275	(14)
S. Russ Price
William E. Mitch
Introduction	275	(1)
The ubiquitin-proteasome pathway	275	(5)
Ubiquitin-like modifier proteins (UBLs)	280	(1)
Gebetic abnormalities involving the ubiquitin-proteasome system	280	(5)
Summary	285	(4)
Index	289