Medical Genetics - V. M. Zaporozhan 2005

Clinical-genealogical method
Review questions for Chapter 4

1. What do the terms genealogy, proband, and sibs mean?

2. The Significance of the Clinical-Genealogical Method.

3. Specifics of taking a genealogical history.

4. Genealogical symbols. Rules for graphic pedigree construction.

5. Characteristic Features of pedigrees with autosomal dominant, autosomal recessive, and Sex-Linked Inheritance patterns.

6. Features of pedigrees with Mitochondrial Inheritance.

Self-assessment and study questions

Task 1

Choose one answer.

1. Sibs are:

A. Parents of the proband

B. Children of the proband

C. Brothers and sisters of the proband

D. Relatives of the proband personally examined by a medical geneticist

2. The parents of an affected child are healthy, but similar conditions occur in the patient's siblings (regardless of sex). This is most characteristic of the following inheritance pattern:

A. Autosomal dominant

B. Autosomal recessive

C. X-linked recessive

D. X-linked dominant

E. Mitochondrial

3. A pedigree with an Autosomal dominant inheritance pattern is characterized by:

A. The trait is inherited "vertically": an affected child usually has one affected parent

B. Males and females are affected with equal frequency; the risk of having an affected child from heterozygous parents is 25 %

C. An affected father passes the trait to 100 % of his daughters and never to his sons

D. Males are predominantly affected; if the mother is heterozygous, 50 % of sons may be affected

E. Males are predominantly affected; 100% of sons inherit the condition from an affected father

4. A pedigree with Autosomal Recessive Inheritance is characterized by:

A. The trait is inherited vertically: an affected child usually has one affected parent

B. Females and males are affected with equal frequency; the risk of having an affected child from heterozygous parents is 25%

C. The trait is inherited by 100% of daughters and never by sons from an affected father

D. Males are predominantly affected; if the mother is heterozygous, 50% of sons may be affected

E. Males are predominantly affected; 100% of sons inherit the condition from an affected father

5. Which inheritance pattern is characterized by predominantly male patients?

A. Autosomal dominant

B. Autosomal recessive

C. X-linked recessive

D. X-linked dominant

E. Mitochondrial

6. Which inheritance pattern shows a higher frequency of affected females?

A. Autosomal dominant

B. Autosomal recessive

C. X-linked recessive

D. X-linked dominant

E. Mitochondrial

7. Information regarding THE ORIGIN OF spouses and their parents from the same or closely located geographic areas may indicate the following type of disease inheritance:

A. Autosomal dominant

B. Autosomal recessive

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Fig. 4.13. Family pedigree with three cases of Achondroplasia in a single generation (a healthy man from his first marriage to a healthy woman has two daughters with achondroplasia — II,1 and II,3; and from his second marriage to a healthy woman — a daughter with achondroplasia — II,4)

C. X-linked recessive

D. X-linked dominant

E. Mitochondrial

8. The figure (Fig. 4.13) shows the pedigree of a family with 3 children suffering from achondroplasia, born to a healthy father from two marriages with healthy women. Achondroplasia is an autosomal dominant disorder with 100% Gene penetrance. The most likely explanation for the birth of three children with achondroplasia in this family is:

A. Germline mosaicism in the father

B. Spontaneous de novo germline Mutations in the father

C. The result of somatic mutations in the children during embryonic development

D. Uniparental disomy — inheritance of two homologous Chromosomes from the father

E. Variable gene expressivity

9. The figure (Fig. 4.14) shows the pedigree of a family, some members of which suffer from Leber's hereditary optic neuropathy. Which inheritance pattern is most characteristic of such a pedigree?

A. Autosomal dominant

B. Autosomal recessive

C. X-linked recessive

D. X-linked dominant

E. Mitochondrial

10. If the first child of healthy parents is born with phenylketonuria (an autosomal recessive trait), the geneticist's most likely Conclusion is:

Fig. 4.14. Pedigree of a family, some members of which suffer from Leber's hereditary optic neuropathy

A. This is the result of a somatic mutation in the affected child

B. This is the result of a new germline mutation in one of the parents

C. Both parents are heterozygous carriers of the recessive pathological gene (both Aa)

D. The mother or father is heterozygous for a dominant pathological gene with incomplete penetrance

E. This is the result of a chromosomal mutation in one of the parents

Task 2

Construct a pedigree.

1. The proband is a healthy 23-year-old woman who consulted a medical genetics clinic for Genetic Counseling regarding her future offspring. The proband has two healthy brothers, as well as a brother and a sister suffering from alkaptonuria. The proband's mother is healthy and has a healthy sister and brother. The proband's father has alkaptonuria and is a first cousin of his wife. He has a healthy brother and sister. The paternal grandmother was affected and was married to her healthy first cousin. The maternal grandmother and grandfather are healthy; the grandfather's parents are also healthy, with the grandfather's mother being the full sister of the proband's paternal grandfather. The proband's husband is healthy, 25 years old. His mother, father, and two brothers are healthy. There is no history of alkaptonuria in his family. Determine the inheritance pattern of alkaptonuria. Calculate the risk of the proband having affected children.