Chapter 4 Pedigree Analysis in Human Genetics. Chapter 4 Human Heredity by Michael Cummings 2006 Brooks/Cole-Thomson Learning

Transcription

1 Chapter 4 Pedigree Analysis in Human Genetics

2 Mendelian Inheritance in Humans Pigmentation Gene and Albinism Fig. 3.14

3 Two Genes Fig. 3.15

4 The Inheritance of Human Traits Difficulties Long generation time Data must be obtained from offspring produced Experimental matings are not possible Limited sample size

5 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

6 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

7 Catalogs of Genetic Traits Figure 4.4 Fig. 4.4

8 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

9 Pedigree Symbols Fig. 3.16

10 Proband First affected family member who seeks medical attention for a genetic disorder

11 Autosomal recessive Fig. 4.5

12 Rare recessive trait I 1 2 aa 1 2 II III aa aa 2 3 5

13 Rare recessive trait I 1 2 aa 1 2 II 1 Aa 2 3 Aa III aa aa 2 3 5

14 Rare recessive trait I AA? 1 2 aa Aa? 1 2 Aa? II Aa 1 Aa 2 3 Aa III aa aa 2 3 5

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16 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

17 Molecular Basis for Cystic Fibrosis Gene located on chromosome 7 Cloned in 1989 (Tsui & Collins) Fig. 4.8

18 Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) CFTR regulates flow of chloride ions across the plasma membrane Reduces fluid in glandular secretions Fig. 4.9

19 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

20 Sickle Cell Anemia Many systems are affected Lethal as homozygous recessive Heterozygotes generally unaffected Confers resistance to malaria parasite High frequency in populations where malaria is found Fig. 4.11

21 Sickle-cell Syndrome Hbα gene Hbβ gene Wild-type Hbβ = A allele Sickle-cell allele Hbβ = S allele β α α β α αaa Wild type α αas Carrier α αss Affected α Α α Α Three kinds of hemoglobins S α α S

22 Carrier (ααas) Polypeptides: α, A and S Α α α Α S α α Α S α α S

23 Normal Carrier Affected Dominance Hb production AA AS SS Codominant RBC shape Normal Normal Sickle A -dominant S - recessive Malaria resistance Normal Resistant Resistant S - dominant A - recessive

24 Autosomal Dominant Traits Heterozygotes and homozygous dominant individuals are affected Affected offspring have at least one affected parent Equal number of males and females

25 Autosomal Dominant Fig. 4.12