Chapter 4 Pedigree Analysis in Human Genetics · 2017. 10. 20. · Pedigree Analysis •Pedigree is an orderly presentation of family information •First step in studying the inheritance

Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning

Chapter 4Pedigree Analysis in Human Genetics


Mendelian Inheritance in HumansPigmentation Gene and Albinism

Fig. 3.14


TwoGenes

Fig. 3.15


The Inheritance of Human Traits

Difficulties• Long generation time• Data must be obtained from

offspring produced• Experimental matings are not

possible• Limited sample size


Pedigree Analysis

• Pedigree is an orderly presentationof family information

• First step in studying the inheritanceof traits

• Important in predicting genetic risk• May be incomplete due to difficulties

collecting information


Pedigree Analysis

• Construct pedigree using availableinformation

• Rule out all patterns of inheritancethat are inconsistent with the data

• May not have enough information toidentify the mode of inheritance

• Some genetic disorders may havemore than one pattern of inheritance


Catalogs of Genetic Traits

Figure 4.4

Fig. 4.4


Autosomal Recessive Traits

• For rare traits most affected individualshave unaffected parents

• Offspring of two affected individualsare affected

• Expressed in males and females equally• In rare traits unaffected parents with

affected offspring may be related to eachother


PedigreeSymbols

Fig. 3.16


Proband

• First affected familymember who seeksmedical attention for agenetic disorder


Autosomal recessive

Fig. 4.5


1 2

1

2 3 5

32 II

I

III

Rare recessive trait

1 2aa

aa aa


1 2

1

2 3 5

32 II

I

III


aa

Aa

1 2

Aa

aa aa


1 2

1

2 3 5

32 II

I

III


aa

AaAa

1 2

Aa

aa aa

AA? Aa? Aa?



Cystic Fibrosis Is an Example of anAutosomal Recessive Trait

• Disabling and fataldisorder

• Affects sweatglands and glandsthat producemucus anddigestive enzymes

Fig. 4.6


Molecular Basis for Cystic Fibrosis

• Gene located onchromosome 7

• Cloned in 1989• (Tsui & Collins)

Fig. 4.8


Cystic Fibrosis TransmembraneConductance Regulator (CFTR)

• CFTR regulatesflow of chlorideions across theplasmamembrane

• Reduces fluid inglandularsecretions Fig. 4.9


Sickle Cell Anemia Is anAutosomal Recessive Trait

• Hemoglobin is an oxygen transportmolecule in red blood cells (RBC)

• Sickle cell hemoglobin is abnormal andcauses RBCs to become crescent or sickleshaped

• RBCs are fragile• It is difficult to maintain normal oxygen

carrying capacity


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


Sickle-cell Syndrome

•Hbα gene•Hbβ gene•Wild-type Hbβ = A allele•Sickle-cell allele Hbβ = S allele

α

β α

β

Wild type α αAA

αΑ α

Α

α αSSAffected

ααS

S

α αAS

Three kindsof hemoglobins

Carrier


Carrier (ααAS)

Polypeptides: α, A and S

ΑS

Αα

αα

α

αα

Α

SS


Normal Carrier Affected Dominance

Hb production AA AS SS Codominant

RBC shape Normal Normal Sickle A -dominantS - recessive

Malaria resistance Normal Resistant Resistant S - dominantA - recessive


Autosomal Dominant Traits

• Heterozygotes and homozygousdominant individuals are affected

• Affected offspring have at least oneaffected parent

• Equal number of males and females


Autosomal Dominant

Fig. 4.12

Documents

Chapter 4 Pedigree Analysis in Human Genetics · 2017. 10. 20. · Pedigree Analysis •Pedigree is an orderly presentation of family information •First step in studying the inheritance