1. Pedigree Analysis, Applications, and Genetic Testing
Benjamin A. Pierce
GENETICS
A Conceptual Approach
SIXTH EDITION
CHAPTER 6
Pedigree Analysis, Applications, and Genetic Testing
© 2017 W. H. Freeman and Company

2. Fingerprints are unique to each person
Fingerprints are unique to each person. A few people have a condition known as adermatoglyphia (ADG), in which fingerprints are completely absent; this condition is inherited as an autosomal dominant trait. Shown here is a human fingerprint superimposed on DNA sequence information. [Phanie/Science Source.]

3. 6.1 Pedigree of Swiss family with adermatoglyphia (absence of fingerprints). Squares represent males; circles represent females. Colored squares and circles are people with adermatoglyphia.

4. 6.1 The Study of Genetics in Humans Is Constrained by Special Features of Human Biology and Culture
Controlled mating not possible
Long generation time
Small family size

5. 6.2 Geneticists Often Use Pedigrees to Study the Inheritance of Characteristics in Humans
Pedigree: pictorial representation of a family history; a family tree that outlines the inheritance of one or more characteristics.
Proband: the person from whom the pedigree is initiated

6. 6.2 Standard symbols are used in pedigrees.

7. 6. 3 Pedigree of a person with Waardenburg syndrome
6.3 Pedigree of a person with Waardenburg syndrome. The proband (P) is the person from whom this pedigree is initiated. (a) Waardenburg syndrome is inherited as an autosomal dominant trait. (b) The syndrome is characterized by deafness, fair skin, visual problems, and a white forelock. [Part b: Courtesy of Guy Rowland.]

8. 6.2 Geneticists Often Use Pedigrees to Study the Inheritance of Characteristics in Humans
Autosomal recessive traits: Fig. 6.4
Autosomal dominant traits: Fig. 6.5
X-linked recessive traits: Figs. 6.7 and 6.8
X-linked dominant traits: Fig. 6.9
Y-linked traits: Fig. 6.10

9. 6.4 Autosomal recessive traits normally appear with equal frequency in both sexes and seem to skip generations.

10. 6.5 Autosomal dominant traits normally appear with equal frequency in both sexes and do not skip generations.

11. 6. 6 Low-density lipoprotein (LDL) particles transport cholesterol
6.6 Low-density lipoprotein (LDL) particles transport cholesterol. The LDL receptor moves LDL from the bloodstream through the cell membrane into the cytoplasm.

12. 6.7 X-linked recessive traits appear more often in males than in females and are not passed from father to son.

13. 6. 8 Classic hemophilia is inherited as an X-linked recessive trait
6.8 Classic hemophilia is inherited as an X-linked recessive trait. This pedigree is of hemophilia in the royal families of Europe.

14. 6. 9 X-linked dominant traits affect both males and females
6.9 X-linked dominant traits affect both males and females. An affected male must have an affected mother.

15. 6.10 Y-linked traits appear only in males and are passed from a father to all his sons.

16. TABLE 6.1
Pedigree characteristics of autosomal recessive, autosomal dominant, X-linked recessive, X-linked dominant, and Y-linked traits
Autosomal Recessive Trait
1. Usually appears in both sexes with equal frequency.
2. Tends to skip generations.
3. Affected offspring are usually born to unaffected parents.
4. When both parents are heterozygous, approximately onefourth of the offspring will be affected.
5. Appears more frequently among the children of consanguineous marriages.

17. TABLE 6.1
Pedigree characteristics of autosomal recessive, autosomal dominant, X-linked recessive, X-linked dominant, and Y-linked traits
Autosomal Dominant Trait
1. Usually appears in both sexes with equal frequency.
2. Both sexes transmit the trait to their offspring.
3. Does not skip generations.
4. Affected offspring must have an affected parent unless they possess a new mutation.
5. When one parent is affected (heterozygous) and the other parent is unaffected, approximately half of the offspring will be affected.
6. Unaffected parents do not transmit the trait.

18. TABLE 6.1
Pedigree characteristics of autosomal recessive, autosomal dominant, X-linked recessive, X-linked dominant, and Y-linked traits
X-Linked Recessive Trait
1. Usually more males than females are affected.
2. Affected sons are usually born to unaffected mothers; thus, the trait skips generations.
3. Approximately half of a carrier (heterozygous) mother’s sons are affected.
4. Never passed from father to son.
5. All daughters of affected fathers are carriers.

19. TABLE 6.1
Pedigree characteristics of autosomal recessive, autosomal dominant, X-linked recessive, X-linked dominant, and Y-linked traits
X-Linked Dominant Trait
1. Both males and females are usually affected; often, more females than males are affected.
2. Does not skip generations. Affected sons must have an affected mother; affected daughters must have either an affected mother or an affected father.
3. Affected fathers pass the trait to all their daughters.
4. Affected mothers (if heterozygous) pass the trait to half of their sons and half of their daughters.

20. TABLE 6.1
Pedigree characteristics of autosomal recessive, autosomal dominant, X-linked recessive, X-linked dominant, and Y-linked traits
Y-Linked Trait
1. Only males are affected.
2. Passed from father to all sons.
3. Does not skip generations.

21. Concept Check 1
Autosomal recessive traits often appear in pedigrees in which there have been consanguine mating, because these traits
a. tend to skip generations.
b. appear only when both parents carry a copy of the gene for the trait, which is more likely when the parents are related.
c. usually arise in children born to parents who are unaffected.
d. appear equally in males and females.

22. Concept Check 1
Autosomal recessive traits often appear in pedigrees in which there have been consanguine mating, because these traits
a. tend to skip generations.
b. appear only when both parents carry a copy of the gene for the trait, which is more likely when the parents are related.
c. usually arise in children born to parents who are unaffected.
d. appear equally in males and females.

23. Concept Check 2
How could you distinguish between an autosomal recessive trait with higher penetrance in males and an X-linked recessive trait?

24. Concept Check 2
How could you distinguish between an autosomal recessive trait with higher penetrance in males and an X-linked recessive trait?
X-linked recessive traits are only passed to sons from mothers, not from fathers.

25. Dizygotic twins = nonidentical twins
6.3 Studying Twins and Adoptions Can Help Assess the Importance of Genes and Environment
Dizygotic twins = nonidentical twins
Monozygotic twins = identical twins
Concordant trait: the trait shared by both members of a twin pair
Concordance: the percentage of twin pairs that are concordant for a trait.
Table 6.2
Twin studies and obesity: Table 6.3

26. 6.11 Two types of twins. Monozygotic twins (a) are identical; dizygotic twins (b) are nonidentical. [Part a: f4foto/Alamy. Part b: Courtesy of Randi Rossignol.]

27. TABLE 6.2 Concordance Monozygotic Dizygotic
Concordance of monozygotic and dizygotic twins for several traits
Trait
Concordance
Monozygotic
Dizygotic
1. Heart attack (males) 39 26
2. Heart attack (females) 44 14
3. Bronchial asthma 47 24
4. Cancer (all sites) 12 15
5. Epilepsy 59 19
6. Death from acute infection
7.9
8.8
7. Rheumatoid arthritis 32 6
8. Multiple sclerosis 28 5
Sources: (1 and 2) B. Havald and M. Hauge, U.S. Public Health Service Publication 1103 (1963), pp. 61–67; (3, 4, 5, and 6) B. Havald and M. Hauge, Genetics and the Epidemiology of Chronic Diseases (U.S. Department of Health, Education, and Welfare, 1965); (7) J. S. Lawrence, Annals of Rheumatic Diseases 26:357–379, 1970; (8) G. C. Ebers et al., American Journal of Human Genetics 36:495,

28. 6.12 Twin studies have shown that asthma is caused by a combination of genetic and environmental factors.

29. Concept Check 3
A trait exhibits 100% concordance in both monozygotic and dizygotic twins. What conclusion can you draw about the role of genetic factors in determining differences in the trait?
a. Genetic factors are extremely important.
b. Genetic factors are somewhat important.
c. Genetic factors are unimportant.
d. Both genetic and environment factors are important.

30. Concept Check 3
A trait exhibits 100% concordance in both monozygotic and dizygotic twins. What conclusion can you draw about the role of genetic factors in determining differences in the trait?
a. Genetic factors are extremely important.
b. Genetic factors are somewhat important.
c. Genetic factors are unimportant.
d. Both genetic and environment factors are important.

31. 6.13 Adoption studies demonstrate that obesity has a genetic influence. [Redrawn with the permission of the New England Journal of Medicine 314:195, 1986.]

32. 6.4 Genetic Counseling and Genetic Testing Provide Information to Those Concerned about Genetic Diseases and Traits
Genetic counseling provides information related to hereditary conditions.

33. Common reasons for seeking genetic counseling
TABLE 6.3
Common reasons for seeking genetic counseling
1. A person knows of a genetic disease in the family.
2. A couple has given birth to a child with a genetic disease, birth defect, or chromosome abnormality.
3. A couple has a child who is intellectually disabled or has a close relative who is intellectually disabled.
4. An older woman becomes pregnant or wants to become pregnant. There is disagreement about the age at which a prospective mother who has no other risk factors should seek genetic counseling; many experts suggest that it should be age 35 or older.
5. Husband and wife are closely related (e.g., first cousins).
6. A couple experiences difficulties achieving a successful pregnancy.
7. A pregnant woman is concerned about exposure to an environmental substance (drug, chemical, or virus) that causes birth defects.
8. A couple needs assistance in interpreting the results of a prenatal or other test.
9. Both prospective parents are known carriers for a recessive genetic disease or both belong to an ethnic group with a high frequency of a genetic disease.

34. TABLE 6.4
Examples of genetic diseases and disorders that can be detected prenatally and the techniques used in their detection
Disorder
Method of Detection
Chromosome abnormalities
Examination of a karyotype from cells obtained by amniocentesis or chorionic villus sampling. Some forms can be detected by DNA analysis of maternal blood.
Cleft lip and palate
Ultrasound
Cystic fibrosis
DNA analysis of cells obtained by amniocentesis or chorionic villus sampling
Dwarfism
Ultrasound or X-ray; some forms can be detected by DNA analysis of cells obtained by amniocentesis or chorionic villus sampling
Hemophilia
Fetal blood sampling* or DNA analysis of cells obtained by amniocentesis or chorionic villus sampling
Lesch–Nyhan syndrome
Biochemical tests on cells obtained by amniocentesis or chorionic villus sampling
Neural-tube defects
Initial screening with maternal blood test, followed by biochemical tests on amniotic fluid obtained by amniocentesis or by the detection of birth defects with the use of ultrasound
Osteogenesis imperfecta
Ultrasound or X-ray (brittle bones)
Phenylketonuria
Sickle-cell anemia
Tay–Sachs disease
*A sample of fetal blood is obtained by inserting a needle into the umbilical cord.

35. 6.14 Ultrasonography can be used to detect some genetic disorders in a fetus and to locate the fetus during amniocentesis and chorionic villus sampling. [PhotoDisc/Media Bakery.]

36. 6.15 Amniocentesis is a procedure for obtaining fetal cells for genetic testing.

37. 6.16 Chorionic villus sampling (CVS) is another procedure for obtaining fetal cells for genetic testing.

38. TABLE 6.5
Genetic conditions recommended for mandatory screening by the American College of Medical Genetics
Medium-chain acyl-CoA dehydrogenase deficiency
Trifunctional protein deficiency
Congenital hypothyroidism
Multiple carboxylase deficiency
Phenylketonuria
Methylmalonic acidemia (mutase deficiency)
Biotinidase deficiency
Homocystinuria (due to cystathionine β synthase deficiency)
Sickle-cell anemia (Hb SS disease)
3-Methylcrotonyl-CoA carboxylase deficiency
Congenital adrenal hyperplasia (21-hydroxylase deficiency)
Hearing loss
Isovaleric acidemia
Methylmalonic acidemia (Cbl A,B)
Very long chain acyl-CoA dehydrogenase deficiency
Propionic acidemia
Maple syrup (urine) disease
Carnitine uptake defect
Galactosemia
β-Ketothiolase deficiency
Hb S/β-thalassemia
Citrullinemia
Hb S/C disease
Argininosuccinic acidemia
Long-chain l-3-hydroxyacyl-CoA dehydrogenase deficiency
Tyrosinemia type I
Glutaric acidemia type I
Cystic fibrosis
3-Hydroxy-3-methyl glutaric aciduria

39. Interpreting Genetic Testing
More than a thousand genetic tests available
Complicated by several factors:
Some diseases caused by numerous mutations
Incomplete penetrance and environmental factors

40. Genetic Discrimination and Privacy
Many new genetics tests
1970s: African Americans carrying sickle-cell trait had difficulty finding employment and health insurance
Genetic Information Nondiscrimination Act