Solutions Manual - Genetic Analysis, 4th Edition by Mark F. Sanders, John L. Bowman
Complete Chapters
A
Latest Edition
Human Hereditary Disease and
Genetic Counseling
Section A.01 Genetics Problem Solving Toolkit
Section A.02 Solutions to End-of-Chapter Problems
Section A.03 Test Yourself
A.01 Genetics Problem Solving Toolkit
Key Terms and Concepts
Mendelian Conditions: Diseases that are caused by mutation of a single gene. The condition may
be recessive or dominant, autosomal or sex-linked. See section 2.6 of the textbook to review autosomal
inheritance and section 3.5 of the textbook to review sex-linked inheritance.
Chromosomal Conditions: Diseases that are caused by an abnormal chromosome number or abnormal
chromosome structure. See Chapter 11 of the textbook for more detailed information on chromosomal
abnormalities that lead to disease.
Multifactorial Conditions: Diseases that are caused by mutations in multiple genes that interact with
each other and with environment factors. See Chapter 17 of the textbook for more detailed information on
multifactorial inheritance.
Carrier Testing: Genetic tests for the presence of recessive mutations performed on unaffected individu-
als (individuals who do not have the recessive mutant phenotype). Carrier testing is done to determine
the risk that an unaffected person will have an affected child. Refer to Type 3 Problems, section 2.02 and
Type 2 Problems, section 3.02 to review solving problems involving carrier testing.
Presymptomatic Testing: Genetic testing of an asympomatic individual for the presence of mutations that
cause disease. Genetic counseling is advised before and after testing because the results of presymptom-
atic tests can have serious psychological impacts on the individual and their family.
Newborn Testing: A routine panel of genetic tests for rare diseases whose effects on the health and devel-
opment of the child can be greatly ameliorated by early intervention. An example is phenylketonuria
(PKU), which is caused by a defect in metabolism of the amino acid, phenylalanine. Undetected, PKU can
lead to serious developmental defects, whereas if detected early, PKU can be essentially negated by a con-
trolled diet.
Prenatal Testing: Testing of DNA from a fetus for Mendelian and/or Chromosomal disorders. Cellular
prenatal DNA can be obtained from amniotic fluid or the chorionic villus (placenta). More recently,
non-invasive DNA screening protocols, which involve the sequencing of trace amounts of fetal DNA
present in maternal blood, have been developed and are their efficacy is being studied.
Genetic Counselor: A professional with specialized training in medical genetics and counseling who
provides assistance to patients concerned with genetic information that pertains to their health.
149
Sanders_4e_A103000418804_SG_CH06_AppA.indd 149 15/06/26 2:41 PM
, 150 CHAPTER A
Immediate Decision Making: This refers to the application of genetic tests to determine whether an indi-
vidual or a fetus has symptoms indicative of genetic disorder to guide decisions concerning an immediate
course of action.
Assessment of Future Risks: This process employs Bayesian probability calculations to determine the
likelihood that a future offspring of a specific couple will have a particular genetic condition.
Bayesian Analysis in Probability Calculations: Bayesian analyses are used to calculate the probability
that an individual or unborn child has a specific genotype using known or inferred genotype information
from a pedigree analysis (conditional probability) and information on the frequency of that genotype in
the general population (prior probability).
Prior Probability of a Genotype: This is the probability that an individual has a specific genotype based
solely on the frequency of the genotype in the appropriate population and no additional information. The
prior probability of a genotype is the same as the population frequency of that genotype.
Conditional Probability of a Genotype: This is the probability that an individual has a specific genotype
based on information inferred from analysis of relatives (pedigree analysis).
Joint Probability of a Genotype: This is the sum or product of two or more probability calculations. For
example, the probability that a man and woman of unknown genotypes will have a child with an autoso-
mal recessive condition is the product of the probability that the man is a heterozygous carrier, the prob-
ability that the woman is a heterozygous carrier, and the probability that two heterozygous carriers will
have an affected child.
Ethical, Legal and Social Implications of the Human Genome Project (ELSI): An initiative funded by
the Human Genome Project to study the legal, ethical and social implications of information obtained
from the sequence and analysis of the human genome and the personal genome of many citizens. The
ELSI focused on four areas of investigation: genetic research; genetic health care; social implications of
genetics and genomics; and the legal, regulatory and public policy issues.
A.02 Solutions to End-of-Chapter Problems
1a. The Prior probability is the Mendelian risk that a person is a heterozygous carrier of a recessive
condition. It is the same as the frequency of carriers in the population.
1b. An obligate carrier is a person who, based on family history, must be a heterozygous carrier of a
recessive mutant allele.
1c. The probability that the healthy brother of a woman with an autosomal recessive condition is a
heterozygous carrier is 66.7%.
1d. The consultand is the person receiving genetic counseling.
1e. The probability that the son of a woman with an autosomal recessive condition is a heterozygous
carrier (given no additional information) is 50%.
2a. The affected gene in Tay-Sachs disease is referred to as HEXA, which stands for the hexoseamini-
dase A gene, and it is located on chromosome 15, at 15q23.
2b. Tay-Sachs disease is most frequently found in infants of Ashkenazi Jewish ancestry. The fre-
1
quency of carriers in North American Jews is about 45 or 2.2 % .
2c. The affected gene in Cystic Fibrosis is referred to as CFTR, which stands for the Cystic Fibrosis
Transmembrane Regulator, and it is located on chromosome 7, at 7q31.2.
2d. The most common mutation in the CF gene is called ∆F508, which is a deletion of the 508th codon
in the CFTR coding sequence, which removes a single phenylalanine amino acid from the CFTR
protein.
Sanders_4e_A103000418804_SG_CH06_AppA.indd 150 15/06/26 2:41 PM
, Human Hereditary Disease and Genetic Counseling 151
3. The problem indicates that the consultands are concerned about the possibility of having a child
with a genetic disorder because members of the woman’s family, including her father, had a
condition that might have a genetic basis. Because specific information concerning this potential
genetic condition is lacking, the first recommendation would be for the consultands to contact the
woman’s family and obtain more specific information about the condition in question and then
take that information to a medical geneticist, who will provide a diagnosis or suggest additional
tests to determine whether or not the condition in question is a genetic disease.
4. The problem states that J.B. and S.B. each have a sibling with the autosomal recessive condition
galactosemia and that they are seeking counseling as to the likelihood that their first child will
have galactosemia. Since neither J.B. nor S.B. have galactosemia, the probability that their first
child will have the disorder depends on the probability that both J.B. and S.B. are heterozygous
carriers. Since neither of J.B.’s parents nor S.B.’s parents had galactosemia, their parents are obli-
gate heterozygous carriers. An unaffected child of heterozygous carrier parents has a 23 condi-
tional probability of being a carrier, therefore; J.B. and S.B. each have a 23 conditional probability
of being carriers. If J.B. and S.B. are both heterozygous carriers, then the probability that their first
son or daughter will have galactosemia is 14. The joint probability that the first child of J.B. and
S.B. will have galactosemia is 23 × 23 × 14 = 36
4
= 19.
5. The problem states that S.R.’s maternal grandfather has X-linked hemophilia A, therefore her
mother is an obligate carrier and S.R. has a 12 chance of being a carrier. If S.R. is a carrier, there is a
1
2 chance that a son of hers will inherit the hemophilia A mutation form her. The joint probability
that a son of S.R. will have hemophilia A is 12 × 12 = 14.
6. The problem states that a newly pregnant woman whose father had Huntington disease (HD) is
seeing counseling on the probability that her child will inherit HD. The woman is 40 years old
and does not yet show signs of the disorder. HD is an autosomal dominant disorder with delayed
age of onset. Assuming that her father was heterozygous for the mutant HD allele, there is a 12
conditional probability that she inherited the mutant allele. If she inherited the mutant allele,
there is a 12 conditional probability that her unborn child will have inherited it. The joint prob-
ability that her unborn child has inherited the mutant HD allele is 12 × 12 = 14. Note: the fact that the
pregnant woman is 40 years old but does not show signs of HD does not affect the probability
that she has inherited the mutant allele because 60% or more of individuals with the mutant HD
allele do not show symptoms at age 40 (see textbook figure Figure 4.11).
A.03 Test Yourself
Problems
1. Match each statement (a – e) with the best answer from the following list: Mendelian condition;
chromosomal condition; multifactorial condition; carrier testing; prenatal testing; newborn testing;
presymptomatic testing.
a. Errors during meiosis cause the formation of abnormal gametes which can contribute to the birth
of a child with a _________.
b. Coronary artery disease is a _________ because it is caused by the combined action of many genes
and by environmental factors.
c. _________ detects inherited disorders early enough to minimize or prevent defects in childhood
development.
d. Cystic Fibrosis is a _________ that shows autosomal recessive inheritance.
e. A man and woman who each have the same autosomal recessive disorder in their family can
have _________ performed to help determine the probability that their first child will be born with
the disorder.
f. _________ can be performed to determine whether an unborn fetus has a genetic condition.
Sanders_4e_A103000418804_SG_CH06_AppA.indd 151 15/06/26 2:41 PM
, 152 CHAPTER A
2. Use your web browser to search OMIM using the search terms “autosomal AND dominant”. Report
on the number of items that are found and select one item, indicate the name of gene, its abbrevia-
tion, the chromosomal location of the gene, and one mutation that has been identified that causes the
disease.
3. A white American man, P.M., and a white American woman, J.B., plan on having a child. Neither P.M.
nor J.B. nor their parents exhibit any known Mendelian conditions, however; one of J.B.’s siblings
has Cystic fibrosis (CF), an autosomal recessive disorder. What is the probability that the first child of
P.M. and J.B. will have CF given the prior probability of CF in the white population and J.B.’s family
history of CF? Hint: use OMIM to find the frequency of heterozygous carriers of CF among whites.
Solutions
1a. Errors during meiosis cause the formation of abnormal gametes which can contribute to the birth
of a child with a chromosomal condition.
1b. Coronary artery disease is a multifactorial condition because it is caused by the combined action
of many genes and by environmental factors.
1c. Newborn testing detects inherited disorders early enough to minimize or prevent defects in
childhood development.
1d. Cystic Fibrosis is a Mendelian condition that shows autosomal recessive inheritance.
1e. A man and woman who each have the same autosomal recessive disorder in their family can
have carrier testing performed to help determine the probability that their first child will be born
with the disorder.
1f. Prenatal testing can be performed to determine whether an unborn fetus has a genetic condition.
2. The problem asks for the number of items that are identified by searching OMIM using the search
terms “autosomal AND dominant”. At the time that this was written, this search identified 4840
items, including the condition, Deafness Autosomal Dominant 52, that is caused by a mutation
in a gene with the same name. The symbol for this gene is DFNA52, and it is located on chromo-
some 5 at 5q31.1-q32. Although 108 SNPs had been identified, none were known to be disease
causing, therefore the mutation responsible for Deafness Autosomal Dominant 52 has not yet
been identified at the time this was written.
3. The problem states that P.M. and J.B. wish to know the probability that their first child will have
Cystic fibrosis (CF). You are told that P.M. has no family history of CF and that J.B.’s sibling has
CF but her parents do not. The probability that their first child will have CF depends on the
probability that both P.M. and J.B. are heterozygous carriers. The prior probability that P.M. is
3
a carrier is 0.03 or 100 , which is the estimated frequency of heterozygous carriers of CF among
white Americans. The conditional probability that J.B. is a carrier is 23 because she is an unaffected
daughter of parents who are obligate carriers. If both P.M. and J.B. are heterozygous carriers, then
the probability that their first child will have CF is 14. The joint probability that the first child of
3 6
P.M. and J.B. is 100 × 32 × 41 = 1200 = 0.005.
Sanders_4e_A103000418804_SG_CH06_AppA.indd 152 15/06/26 2:41 PM
Complete Chapters
A
Latest Edition
Human Hereditary Disease and
Genetic Counseling
Section A.01 Genetics Problem Solving Toolkit
Section A.02 Solutions to End-of-Chapter Problems
Section A.03 Test Yourself
A.01 Genetics Problem Solving Toolkit
Key Terms and Concepts
Mendelian Conditions: Diseases that are caused by mutation of a single gene. The condition may
be recessive or dominant, autosomal or sex-linked. See section 2.6 of the textbook to review autosomal
inheritance and section 3.5 of the textbook to review sex-linked inheritance.
Chromosomal Conditions: Diseases that are caused by an abnormal chromosome number or abnormal
chromosome structure. See Chapter 11 of the textbook for more detailed information on chromosomal
abnormalities that lead to disease.
Multifactorial Conditions: Diseases that are caused by mutations in multiple genes that interact with
each other and with environment factors. See Chapter 17 of the textbook for more detailed information on
multifactorial inheritance.
Carrier Testing: Genetic tests for the presence of recessive mutations performed on unaffected individu-
als (individuals who do not have the recessive mutant phenotype). Carrier testing is done to determine
the risk that an unaffected person will have an affected child. Refer to Type 3 Problems, section 2.02 and
Type 2 Problems, section 3.02 to review solving problems involving carrier testing.
Presymptomatic Testing: Genetic testing of an asympomatic individual for the presence of mutations that
cause disease. Genetic counseling is advised before and after testing because the results of presymptom-
atic tests can have serious psychological impacts on the individual and their family.
Newborn Testing: A routine panel of genetic tests for rare diseases whose effects on the health and devel-
opment of the child can be greatly ameliorated by early intervention. An example is phenylketonuria
(PKU), which is caused by a defect in metabolism of the amino acid, phenylalanine. Undetected, PKU can
lead to serious developmental defects, whereas if detected early, PKU can be essentially negated by a con-
trolled diet.
Prenatal Testing: Testing of DNA from a fetus for Mendelian and/or Chromosomal disorders. Cellular
prenatal DNA can be obtained from amniotic fluid or the chorionic villus (placenta). More recently,
non-invasive DNA screening protocols, which involve the sequencing of trace amounts of fetal DNA
present in maternal blood, have been developed and are their efficacy is being studied.
Genetic Counselor: A professional with specialized training in medical genetics and counseling who
provides assistance to patients concerned with genetic information that pertains to their health.
149
Sanders_4e_A103000418804_SG_CH06_AppA.indd 149 15/06/26 2:41 PM
, 150 CHAPTER A
Immediate Decision Making: This refers to the application of genetic tests to determine whether an indi-
vidual or a fetus has symptoms indicative of genetic disorder to guide decisions concerning an immediate
course of action.
Assessment of Future Risks: This process employs Bayesian probability calculations to determine the
likelihood that a future offspring of a specific couple will have a particular genetic condition.
Bayesian Analysis in Probability Calculations: Bayesian analyses are used to calculate the probability
that an individual or unborn child has a specific genotype using known or inferred genotype information
from a pedigree analysis (conditional probability) and information on the frequency of that genotype in
the general population (prior probability).
Prior Probability of a Genotype: This is the probability that an individual has a specific genotype based
solely on the frequency of the genotype in the appropriate population and no additional information. The
prior probability of a genotype is the same as the population frequency of that genotype.
Conditional Probability of a Genotype: This is the probability that an individual has a specific genotype
based on information inferred from analysis of relatives (pedigree analysis).
Joint Probability of a Genotype: This is the sum or product of two or more probability calculations. For
example, the probability that a man and woman of unknown genotypes will have a child with an autoso-
mal recessive condition is the product of the probability that the man is a heterozygous carrier, the prob-
ability that the woman is a heterozygous carrier, and the probability that two heterozygous carriers will
have an affected child.
Ethical, Legal and Social Implications of the Human Genome Project (ELSI): An initiative funded by
the Human Genome Project to study the legal, ethical and social implications of information obtained
from the sequence and analysis of the human genome and the personal genome of many citizens. The
ELSI focused on four areas of investigation: genetic research; genetic health care; social implications of
genetics and genomics; and the legal, regulatory and public policy issues.
A.02 Solutions to End-of-Chapter Problems
1a. The Prior probability is the Mendelian risk that a person is a heterozygous carrier of a recessive
condition. It is the same as the frequency of carriers in the population.
1b. An obligate carrier is a person who, based on family history, must be a heterozygous carrier of a
recessive mutant allele.
1c. The probability that the healthy brother of a woman with an autosomal recessive condition is a
heterozygous carrier is 66.7%.
1d. The consultand is the person receiving genetic counseling.
1e. The probability that the son of a woman with an autosomal recessive condition is a heterozygous
carrier (given no additional information) is 50%.
2a. The affected gene in Tay-Sachs disease is referred to as HEXA, which stands for the hexoseamini-
dase A gene, and it is located on chromosome 15, at 15q23.
2b. Tay-Sachs disease is most frequently found in infants of Ashkenazi Jewish ancestry. The fre-
1
quency of carriers in North American Jews is about 45 or 2.2 % .
2c. The affected gene in Cystic Fibrosis is referred to as CFTR, which stands for the Cystic Fibrosis
Transmembrane Regulator, and it is located on chromosome 7, at 7q31.2.
2d. The most common mutation in the CF gene is called ∆F508, which is a deletion of the 508th codon
in the CFTR coding sequence, which removes a single phenylalanine amino acid from the CFTR
protein.
Sanders_4e_A103000418804_SG_CH06_AppA.indd 150 15/06/26 2:41 PM
, Human Hereditary Disease and Genetic Counseling 151
3. The problem indicates that the consultands are concerned about the possibility of having a child
with a genetic disorder because members of the woman’s family, including her father, had a
condition that might have a genetic basis. Because specific information concerning this potential
genetic condition is lacking, the first recommendation would be for the consultands to contact the
woman’s family and obtain more specific information about the condition in question and then
take that information to a medical geneticist, who will provide a diagnosis or suggest additional
tests to determine whether or not the condition in question is a genetic disease.
4. The problem states that J.B. and S.B. each have a sibling with the autosomal recessive condition
galactosemia and that they are seeking counseling as to the likelihood that their first child will
have galactosemia. Since neither J.B. nor S.B. have galactosemia, the probability that their first
child will have the disorder depends on the probability that both J.B. and S.B. are heterozygous
carriers. Since neither of J.B.’s parents nor S.B.’s parents had galactosemia, their parents are obli-
gate heterozygous carriers. An unaffected child of heterozygous carrier parents has a 23 condi-
tional probability of being a carrier, therefore; J.B. and S.B. each have a 23 conditional probability
of being carriers. If J.B. and S.B. are both heterozygous carriers, then the probability that their first
son or daughter will have galactosemia is 14. The joint probability that the first child of J.B. and
S.B. will have galactosemia is 23 × 23 × 14 = 36
4
= 19.
5. The problem states that S.R.’s maternal grandfather has X-linked hemophilia A, therefore her
mother is an obligate carrier and S.R. has a 12 chance of being a carrier. If S.R. is a carrier, there is a
1
2 chance that a son of hers will inherit the hemophilia A mutation form her. The joint probability
that a son of S.R. will have hemophilia A is 12 × 12 = 14.
6. The problem states that a newly pregnant woman whose father had Huntington disease (HD) is
seeing counseling on the probability that her child will inherit HD. The woman is 40 years old
and does not yet show signs of the disorder. HD is an autosomal dominant disorder with delayed
age of onset. Assuming that her father was heterozygous for the mutant HD allele, there is a 12
conditional probability that she inherited the mutant allele. If she inherited the mutant allele,
there is a 12 conditional probability that her unborn child will have inherited it. The joint prob-
ability that her unborn child has inherited the mutant HD allele is 12 × 12 = 14. Note: the fact that the
pregnant woman is 40 years old but does not show signs of HD does not affect the probability
that she has inherited the mutant allele because 60% or more of individuals with the mutant HD
allele do not show symptoms at age 40 (see textbook figure Figure 4.11).
A.03 Test Yourself
Problems
1. Match each statement (a – e) with the best answer from the following list: Mendelian condition;
chromosomal condition; multifactorial condition; carrier testing; prenatal testing; newborn testing;
presymptomatic testing.
a. Errors during meiosis cause the formation of abnormal gametes which can contribute to the birth
of a child with a _________.
b. Coronary artery disease is a _________ because it is caused by the combined action of many genes
and by environmental factors.
c. _________ detects inherited disorders early enough to minimize or prevent defects in childhood
development.
d. Cystic Fibrosis is a _________ that shows autosomal recessive inheritance.
e. A man and woman who each have the same autosomal recessive disorder in their family can
have _________ performed to help determine the probability that their first child will be born with
the disorder.
f. _________ can be performed to determine whether an unborn fetus has a genetic condition.
Sanders_4e_A103000418804_SG_CH06_AppA.indd 151 15/06/26 2:41 PM
, 152 CHAPTER A
2. Use your web browser to search OMIM using the search terms “autosomal AND dominant”. Report
on the number of items that are found and select one item, indicate the name of gene, its abbrevia-
tion, the chromosomal location of the gene, and one mutation that has been identified that causes the
disease.
3. A white American man, P.M., and a white American woman, J.B., plan on having a child. Neither P.M.
nor J.B. nor their parents exhibit any known Mendelian conditions, however; one of J.B.’s siblings
has Cystic fibrosis (CF), an autosomal recessive disorder. What is the probability that the first child of
P.M. and J.B. will have CF given the prior probability of CF in the white population and J.B.’s family
history of CF? Hint: use OMIM to find the frequency of heterozygous carriers of CF among whites.
Solutions
1a. Errors during meiosis cause the formation of abnormal gametes which can contribute to the birth
of a child with a chromosomal condition.
1b. Coronary artery disease is a multifactorial condition because it is caused by the combined action
of many genes and by environmental factors.
1c. Newborn testing detects inherited disorders early enough to minimize or prevent defects in
childhood development.
1d. Cystic Fibrosis is a Mendelian condition that shows autosomal recessive inheritance.
1e. A man and woman who each have the same autosomal recessive disorder in their family can
have carrier testing performed to help determine the probability that their first child will be born
with the disorder.
1f. Prenatal testing can be performed to determine whether an unborn fetus has a genetic condition.
2. The problem asks for the number of items that are identified by searching OMIM using the search
terms “autosomal AND dominant”. At the time that this was written, this search identified 4840
items, including the condition, Deafness Autosomal Dominant 52, that is caused by a mutation
in a gene with the same name. The symbol for this gene is DFNA52, and it is located on chromo-
some 5 at 5q31.1-q32. Although 108 SNPs had been identified, none were known to be disease
causing, therefore the mutation responsible for Deafness Autosomal Dominant 52 has not yet
been identified at the time this was written.
3. The problem states that P.M. and J.B. wish to know the probability that their first child will have
Cystic fibrosis (CF). You are told that P.M. has no family history of CF and that J.B.’s sibling has
CF but her parents do not. The probability that their first child will have CF depends on the
probability that both P.M. and J.B. are heterozygous carriers. The prior probability that P.M. is
3
a carrier is 0.03 or 100 , which is the estimated frequency of heterozygous carriers of CF among
white Americans. The conditional probability that J.B. is a carrier is 23 because she is an unaffected
daughter of parents who are obligate carriers. If both P.M. and J.B. are heterozygous carriers, then
the probability that their first child will have CF is 14. The joint probability that the first child of
3 6
P.M. and J.B. is 100 × 32 × 41 = 1200 = 0.005.
Sanders_4e_A103000418804_SG_CH06_AppA.indd 152 15/06/26 2:41 PM
