Medical genetics Single gene Disorders Lecturer: david saffen Ph. D Laboratory for Molecular Neuropsychiatric Genetics Department of Cellular and Genetic Medicine School of Medicine, Fudan University saffen@fudan.edu.cn
Medical Genetics: Single Gene Disorders Lecturer: David Saffen. Ph.D. Laboratory for Molecular Neuropsychiatric Genetics Department of Cellular and Genetic Medicine School of Medicine, Fudan University saffen@fudan.edu.cn
Outline A Historical Background B. Patterns of inheritance C. Genetic mutations D. Prenatal diagnosis
Outline A. Historical Background B. Patterns of inheritance C. Genetic mutations D. Prenatal diagnosis
A. Historical Background Gregor Mendel Archibald garrod Thomas Hunt Morgan Linus Pauling
A. Historical Background • Gregor Mendel • Archibald Garrod • Thomas Hunt Morgan • Linus Pauling
Gregor Mendel Established the rules of inheritance of discrete traits in plants, providing the foundation for the discovery of the gene and the establishment of the modern science of genetics Mendels laws Law of Segregation Each individual possesses two factors(alleles)for a given trait, which "segregate"during the formation of gametes in such a manner that each gamete contains only one of the factors(alleles). Progeny subsequently receive one factor (allele) from their father and one factor (allele) from their mother 1822-1884; German-speaking Law of Independent Assortment Augustinian friar in Brno, silesia Factors(alleles) for distinct traits are inherited (currently Czech Republic) independently, i.e. the inheritance of a factor(allele)for one trait does not influence the inheritance of a factor (allele)for a second trait
Gregor Mendel 1822-1884; German-speaking Augustinian friar in Brno, Silesia (currently Czech Republic) Established the rules of inheritance of discrete traits in plants, providing the foundation for the discovery of the gene and the establishment of the modern science of genetics Mendel’s Laws: Law of Segregation: Each individual possesses two factors (alleles) for a given trait, which “segregate” during the formation of gametes in such a manner that each gamete contains only one of the factors (alleles). Progeny subsequently receive one factor (allele) from their father and one factor (allele) from their mother Law of Independent Assortment: Factors (alleles) for distinct traits are inherited independently, i.e. the inheritance of a factor (allele) for one trait does not Influence the inheritance of a factor (allele) for a second trait
Archibald garrod Postulated that recessive metabolic disorders resulted fror the inheritance of a defective enzyme from each parent Garrods tetrad: alkaptonuria, cystinuria pentosuria, albinism Phenylalanine Tyros p-Hydrowylphenylpyruwc acid ogenic acd Urine samples from patient +× Homogentsic acid ox 1857-1936 British physician with alkaptonuria. Left (freshly Professor Oxford University voided); right (after 24 h at RT) Maleylacetoacetc acid Published Inborn Errors of Metabolism" in 1908 OH HO OH Cystine stone in the urinary bladder OH O Xylulose accumulates in the urine Cystinuria (caused by defects in the SLC3A1 of patients with pentosuria. and SLC7A9 transporter genes) (caused by L-xylulase deficiency) Albinism (caused by a deficiency of tyrosinase, a enzyme required for the synthesis of melanin)
Archibald Garrod 1857- 1936; British physician Professor Oxford University; Published Inborn Errors of Metabolism” in 1908 Postulated that recessive metabolic disorders resulted from the inheritance of a defective enzyme from each parent. Garrod’s tetrad: alkaptonuria, cystinuria, pentosuria, albinism Urine samples from patient with alkaptonuria. Left (freshly voided); right (after 24 h at RT) Albinism (caused by a deficiency of tyrosinase, a enzyme required for the synthesis of melanin) Cystinuria (caused by defects in the SLC3A1 and SLC7A9 transporter genes) Xylulose accumulates in the urine of patients with pentosuria. (caused by L-xylulase deficiency)