1) Pedigree analysis is a tool used to study inheritance patterns of genetic traits and diseases in human families. It allows inferences about genotypes and predictions about disease risk for offspring. 2) A sample pedigree is presented showing inheritance of cystic fibrosis, an autosomal recessive disease. Affected individuals are marked and generations are numbered. 3) Different categories of inheritance exist, including autosomal recessive/dominant and X-linked recessive/dominant patterns. Autosomal recessive traits are often rare and skip generations while autosomal dominant traits are common in every generation.

1. The Inheritance of
Single-Gene Differences
Human pedigree analysis

2. Pedigree analysis
• Analysis of inheritance in human families
• A very important tool for studying human
inherited diseases
– Allow inferences concerning genotypes in a family or population
– Allows predictions concerning phenotypes of offspring inheriting
a genetic disease (genetic counseling)
• Typically small number of offspring
– Mendelian ratios rarely observed
– this means the normal 3:1 dominant to recessive ratio
doesn’t usually occur.

3. unaffected
male
unaffected
female
affected
male
affected
female
Most common symbols used in creating
a pedigree

4. Other common
signs and symbols
used in pedigree
analysis

5. Sample pedigree - cystic fibrosis
female
male
affected individuals
The roman numerals indicate the generation (I, II or III) and
the numbers show birth order of children (1, 2, 3, 4 etc.)

6. Describe the pedigree on the previous slide
for the following questions:
3.What disease or trait is being shown?
4.Is person I-1 male or female?
5.Has person II-3 mated?
6.How many children do I-1 and I-2 have?
7.Which individuals in this family have cystic fibrosis?
8. Compared to the individuals in generation I, are the individuals
in generation III: children, parents, grandchildren or siblings?

7. Based on the same pedigree, we can determine a reasonable guess
as to what the genotypes of the parents and offspring are:
a. Assuming this is a recessive gene,
we know that II-3 and III-4 must be
“aa.”
b. Therefore both parents of these
offspring must have given an “a”
allele.
c. So, I-1, I-2, II-4 and II-5 must each
have one “a” in their genotypes.
d. Since I-1, I-2, II-4 and II-5 don’t
have the disease, their other allele
must be “A.”
e. All the rest of the people could be
either AA or Aa.

8. I-1 I-2
II-1
II-2 II-3 II-4 II-5
1. What are the genotypes or possible genotypes for each
individual in this family?
2. Use the letter B to represent dominant alleles and b to
represent recessive alleles.

9. Categories of inheritance
• Autosomal means inherited on chromosome 1-22 while sex-
linked means inherited on either X or Y chromosome.
• Autosomal recessive
– e.g., PKU, Tay-Sachs, albinism
• Autosomal dominant
– e.g., Huntington’s Disease
• X-linked recessive (meaning this allele is found on only the X
chromosome: can be in males or females)
– e.g., color-blindness, hemophilia
• X-linked dominant (meaning this allele is found on X
chromosomes; can be in males or females)
– e.g., hypophosphatemia
• Y-linked (meaning the allele is found on the Y chromosome
and can only be in males)

10. Autosomal recessive traits
• Trait is rare in the pedigree
• Trait often skips generations
(hidden in heterozygous
carriers)
• Trait affects males and
females equally
• Possible diseases include:
Cystic fibrosis, Sickle cell
anemia, Phenylketonuria
(PKU), Tay-Sachs disease

11. Autosomal dominant pedigrees
• Trait is common in the pedigree
• Trait is found in every generation
• Affected individuals transmit the trait to about 1/2 of their
children (regardless of sex)

12. Autosomal dominant traits
There are few autosomal
dominant human
diseases (why?), but
some rare traits have this
inheritance pattern
For example:
achondroplasia (a
sketelal disorder causing
dwarfism)

13. - Half the people in the
Venezuelan village of
Barranquitas are
affected
- A large-scale pedigree
analysis was conducted
including 10,000 people
- Example for one
particular family:
Huntington’s disease: an example of AD disorder

14. X-linked recessive pedigrees
• Trait is rare in pedigree
• Trait skips generations
• Affected fathers DO NOT
pass to their sons
• Males are more often affected
than females
• Females are carriers (passed
from mom to son)

15. Hemophilia: an example of X-linked recessive
disorder

16. X-linked recessive traits
ex. Hemophilia in European royalty

17. X-linked recessive traits
ex. Glucose-6-Phosphate Dehydrogenase deficiency
• hemolytic disorder causes jaundice in infants and (often fatal)
sensitivity to fava beans in adults
• the most common enzyme disorder
worldwide, especially in those of
Mediterranean ancestry
• may give the individual resistance to
malaria

18. X-linked dominant pedigrees
• Trait is common in pedigree
• Affected fathers pass to ALL of their daughters
• Males and females are equally likely to be affected

19. X-linked dominant diseases
• X-linked dominant diseases are extremely unusual
• Often, they are lethal (before birth) in males and only seen in
females
ex. incontinentia pigmenti (skin lesions)
ex. X-linked rickets (bone lesions)

20. Pedigree Analysis in real life
Remember:
• dominant traits may be rare in a population
• recessive traits may be common in a population
• alleles may come into the pedigree from 2 sources
• mutation happens
• often traits are more complex
• affected by environment & other genes