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

I
aa
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

I
aa
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
•Hbβ gene
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