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Chapter 4 Pedigree Analysis in Human Genetics

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Chapter 4 Pedigree Analysis in Human Genetics Chapter 4 Pedigree Analysis in Human Genetics Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning Mendelian Inheritance in Humans Pigmentation Gene and Albinism Fig. 3.14 Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning Two Genes Fig. 3.15 Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning The Inheritance of Human Traits Difficulties • Long generation time • Data must be obtained from offspring produced • Experimental matings are not possible • Limited sample size Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning Pedigree Analysis • Pedigree is an orderly presentation of family information • First step in studying the inheritance of traits • Important in predicting genetic risk • May be incomplete due to difficulties collecting information Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning Pedigree Analysis • Construct pedigree using available information • Rule out all patterns of inheritance that are inconsistent with the data • May not have enough information to identify the mode of inheritance • Some genetic disorders may have more than one pattern of inheritance Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning Catalogs of Genetic Traits Figure 4.4 Fig. 4.4 Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning Autosomal Recessive Traits • For rare traits most affected individuals have unaffected parents • Offspring of two affected individuals are affected • Expressed in males and females equally • In rare traits unaffected parents with affected offspring may be related to each other Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning Pedigree Symbols Fig. 3.16 Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning Proband • First affected family member who seeks medical attention for a genetic disorder Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning Autosomal recessive Fig. 4.5 Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning Rare recessive trait aa I 1 2 1 2 II 1 2 3 III aa aa 2 3 5 Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning Rare recessive trait aa I 1 2 1 2 II Aa Aa 1 2 3 III aa aa 2 3 5 Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning Rare recessive trait AA? aa Aa? Aa? I 1 2 1 2 II Aa Aa Aa 1 2 3 III aa aa 2 3 5 Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning Cystic Fibrosis Is an Example of an Autosomal Recessive Trait • Disabling and fatal disorder • Affects sweat glands and glands that produce mucus and digestive enzymes Fig. 4.6 Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning Molecular Basis for Cystic Fibrosis • Gene located on chromosome 7 • Cloned in 1989 • (Tsui & Collins) Fig. 4.8 Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) • CFTR regulates flow of chloride ions across the plasma membrane • Reduces fluid in glandular secretions Fig. 4.9 Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning Sickle Cell Anemia Is an Autosomal Recessive Trait • Hemoglobin is an oxygen transport molecule in red blood cells (RBC) • Sickle cell hemoglobin is abnormal and causes RBCs to become crescent or sickle shaped • RBCs are fragile • It is difficult to maintain normal oxygen carrying capacity Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning Sickle Cell Anemia Fig. 4.11 • Many systems are affected • Lethal as homozygous recessive • Heterozygotes generally unaffected • Confers resistance to malaria parasite • High frequency in populations where malaria is found Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning Sickle-cell Syndrome •Hbα gene β α •Hb gene β α β •Wild-type Hbβ = A allele •Sickle-cell allele Hbβ = S allele α αAA α αAS α αSS Wild type Carrier Affected Α α Three kinds S α α Α of hemoglobins α S Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning Carrier (ααAS) Polypeptides: α, A and S Α α S α α Α α Α S α α S Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning Normal Carrier Affected Dominance Hb production AA AS SS Codominant RBC shape Normal Normal Sickle A -dominant S - recessive S - dominant Malaria resistance Normal Resistant Resistant A - recessive Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning Autosomal Dominant Traits • Heterozygotes and homozygous dominant individuals are affected • Affected offspring have at least one affected parent • Equal number of males and females Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning Autosomal Dominant Fig. 4.12 Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning.
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