Download 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
1
2
2
II
3
2
1
aa
III
2
aa
3
Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
5
Rare recessive trait
aa
I
1
1
2
Aa
II
Aa
3
2
1
aa
III
2
2
aa
3
Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
5
Rare recessive trait
I
II
AA?
aa
1
Aa?
1
2
Aa
Aa
3
aa
III
2
2
Aa
2
1
Aa?
aa
3
Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
5
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
Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Fig. 4.9
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
•Hbβ gene
•Wild-type Hbβ = A allele
•Sickle-cell allele Hbβ = S allele
α αAA
α αAS
Wild type
Carrier
Α α
α Α
β α
α
β
α αSS
Affected
Three kinds
of hemoglobins
Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
S α
α S
Carrier (ααAS)
Polypeptides: α, A and S
Α α
α Α
S α
α Α
S α
α S
Chapter 4 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Normal
Hb production
RBC shape
Carrier Affected
Dominance
AA
AS
SS
Codominant
Normal
Normal
Sickle
A -dominant
S - recessive
Resistant
Resistant
S - dominant
A - recessive
Malaria resistance Normal
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