Chapter 4

Question 1

Mendelian inheritance

Answer 1

-refers to the rules for inheritance of monogenic traits as first recognized by Gregor Mendel in the 19th century. -These rules help explain how traits can be inherited from remote ancestors as well as more directly from our parents.

Question 2

monogenic trait
Aka
single-gene trait

Answer 2

-A monogenic trait or single-gene trait is one in which the expression is determined by the input of the two alleles (one from each parent) of a single gene.
-Because alleles segregate, meaning that normally only one allele of a pair is transmitted from each parent to any child, a single gene remains distinct and does not combine with alleles from other genes.
-Thus, inheritance patterns from one family generation to another can be traced.

Question 3

Polygenic traits

Answer 3

-traits or structures that involve the input of more than one gene
-Mendelian rules and patterns do not apply

Question 4

P1 generation

Answer 4

-indicates the initial parental generation of a family or group being observed for a specific trait or traits.
-For example, if you were examining your family history, starting with your great-grandparents, they would be the P1 generation.

Question 5

F generations

Answer 5

-succeeding generations of offspring or progeny produced from the parental generation. Each succeeding generation is designated by a numeric subscript (F1 F2, F3 , etc.)
-Ex. if your great-grandparents are the P1 generation, your grandparents are the F1 your parents are the F2, you and your siblings are the F3 , and your children are the F4 generations.

Question 6

Codominant expression
Aka
Incomplete dominance

Answer 6

-Traits equally expressed
-in codominant inheritance, the phenotype accurately expresses the genotype. (I.e Red flowers must have two red gene alleles (homozygous), pink flowers must have one red gene allele and one white gene allele (heterozygous), and white flowers must have two white gene alleles (homozygous).)

Question 7

Pleiotropy

Answer 7

-pleiotropic gene codes for a substance or a structure that is found in more man one tissue or organ.
- a problem with that gene will result in changes that are expressed in more man one organ or body area.
-Pleiotropy or pleiotropic effects are seen in genes that have autosomal-dominant transmission panerns and in those that have autosomal-recessive transmission patterns.

Question 8

Transmission

Answer 8

-term used to describe how a trait is inherited or passed from one human generation to the next.
-Transmission patterns are determined by examining the way a trait is expressed through several generations of a family.

Question 9

Kindred

Answer 9

-A kindred (sometimes termed a kinship) is the extended family relationships over several generations.

Question 10

Autosomal-DominantTransmission
Figure 4-1

Answer 10

-Autosomal-dominant (AD) single-gene traits have the controlling gene alleles located on an autosomal chromosome.
-The trait is expressed regardless of whether the person is homozygous or heterozygous for the dominant allele. -Criteria for AD patterns of inheritance include the following:
• The trait is found in about equal distribution between male and female family members.
• The trait has no carrier status (the person with even one dominant allele expresses the trait).
• The trait appears in every generation, with clear transmission from parent to child.
• The risk for an affected person who is heterozygous for the dominant allele to pass the trait to his or her
child is 50% with each pregnancy.
• The risk for an affected person who is homozygous for the dominant allele to pass the trait to his or her child is 100% with each pregnancy.
• Unaffected people do not have the allele and have essentially zero risk for transmitting the trait to their
children.
-Figure 4-1 shows a typical pedigree with the transmission of an AD trait.

Question 11

What are two factors that affect the expression of some AD single-gene traits?

Answer 11

Penetrance and expressivity

Question 12

Table 4-4
Three Most Common Mendelian Patterns of Inheritance for Monogenic Traits and Disorders

Question 13

Penetrance

Answer 13

-how often a gene is expressed within a population when it is present.
-Penetrance is calculated by examining a population of people known to have the gene mutation and determining the percentage of people within that population who ever express the condition coded by the gene.
-For an AD genetic disorder that has high penetrance, among 100 individuals who have one allele, nearly 100% will express the disorder.
-Some dominant gene alleles have “reduced” penetrance. This means that a person who has the gene muta- tion has a risk of less than L00% for expressing the gene.

Question 14

Expressivity

Answer 14

-Expressivity is a personal issue (rather than a population issue) in which the degree of gene expression varies by the person who has a dominant gene for a health problem.
-The gene is always expressed, but some people have more severe problems than do others.
-A person with low expression of this problem can transmit the gene to his or her child, who then may have high expression of the disorder. The reverse also is true. A person with high expression can transmit the gene to his or her child, who then may have low expression of the disorder. So degree of expressiviry is not predictable.

Question 15

Autosomal-Recessive Transmission

Answer 15

-Autosomal-recessive (AR) traits have the controlling gene alleles on an autosomal chromosome.
-These traits are expressed only when both alleles are present.
-Figure 4-2 shows a typical pedigree with the transmission of an AR disorder. The trait is expressed only when the person is homozygous for the recessive alleles.
-Criteria for AR patterns of inheritance include the following:
• The trait is found in about equal distribution between male and female family members.
• The trait often appears first in siblings rather than in the parents of affected children.
• The trait may not appear in all generations of any one branch of a family.
• The risk for the children of two affected parents to also be affected is close to 100%.
• About 25% of the members of a family with an AR trait will express the trait or disorder.
• AR traits do have a carrier status in which those individuals who have only one affected allele may not
express any level of the trait .
•Unaffected carriers of AR traits can transmit the trait to their children if their partner is either a carrier or is affected .
• An AR allele may be present in a family for many generations without overt expression.
-The phenotype and genotype are the same for EXPRESSED AR traits and disorders.

Question 16

Carrier
Obligate carrier

Answer 16

-A person who has one mutated allele for a recessive genetic disorder is a carrier.
-Figure 4-3 shows an AR pedigree with affected individuals, unaffected individuals, and carriers identified.
-Remember, that the child of a person who expresses an AR trait will have at least one of the two recessive alleles.
-This person is termed an obligate carrier of that trait even if he or she does not express it.

Question 17

Sex-Linked Inheritance
Y-linked Transmission
Figure 4-4

Answer 17

-Genes on the Y chromosome are termed Y-linked. All males inherit their Y chromosomes from their fathers
(because mothers, being female, do not have them).
-Thus, the unique genes on the Y chromosome are all paternal in origin and are expressed only in males. ‘
-Most of these unique genes are important for male sexual development and fertility.
-This includes penis size and relative fertility in terms of the amount of different types of testosterone produced and rate of spermatogenesis (development of mature, fertile sperm).
-The timing of the onset of puberty in males also appears related to Y-linked inheritance.

Question 18

Sex-Linked Inheritance
X-linked Transmission
X-linked recessive

Answer 18

-Because males have only one X chromosome, they have only one allele for every gene on the X chromosome and thus have only half of the X gene alleles that a female has. -Because these alleles have no corresponding (balancing) allele on the Y chromosome, any X-linked allele in a male is expressed as if it were a dominant allele, a condition known as hemizygosity.
-As a result. X-linked-recessive genes have dominant expression in malesand recessive expression in females.
-Figure 4-5 shows a typical pedigree for an X-linked-recessive trait or disorder, including carrier status. Features of a sex-linked-recessive pattern of inheritance include the following:
• The incidence of the trait (or disorder) is much higher among males in a family than among females (and may be exclusive to males).
• The trait cannot be transmitted from father to son.
• Transmission occurs from an affected father to all daughters (who will be obligate carriers) and from a
carrier mother to both sons and daughters.
• Female carriers have a 50% risk for transmitting the gene to their children with each pregnancy.
• If no sons are born to carrier mothers, the trait may not be expressed overtly for many generations.
• If no daughters are born to affected fathers who have children with noncarrier mothers. the trait is not transmitted further.
• Depending on the disorder, females who are homozygous for an X-linked-disorder gene allele may not
survive pregnancy or will have more severe disease.

Question 19

X-LINKED DOMINANT.

Answer 19

-Rare
-Females express the disorder in heterozygous state
-Males who are hemizygous for the allele are more profoundly affected than are heterozygous females.
-an affected father transmits the disorder to all his daughters (who then express the disorder) and co none of his sons.
-The most notable feature that distinguishes this transmission from that of autosomal recessive is the complete lack of father-co-son transmission.

Question 20

Hemizygosity

Answer 20

any X-linked allele in a male is expressed as if it were a dominant allele

Question 21

X-CHROMOSOME INACTIVATION

Answer 21

-To prevent XX females from having an excessive “dose” of the X chromosome genes coding for somatic cell function, one X chromosome in every somatic cell is randomly inactivated.
-This random inactivation means that, in some cells, the paternally derived X chromosome is inactivated, existing as a Barr body, and only the maternal genes are expressed in those cells.
-In other cells, the maternally derived X chromosome is inactivated, existing as a Barr body, and only the paternal genes are expressed in those cells (Fig. 4-6).

Question 22

probability

Answer 22

A chance based on statistics-it is not an absolute-

Question 23

Punnett square issues

Answer 23

-Issue with Punnett square analysis is that it does not take into account any other factors that may influence the expression of monogenic traits. Other factors that can modify the expression of a monogenic trait or problem include the presence of modifier genes, the environment, and epigenetic influences.

Question 24

Complex traits and diseases
Aka
multifactorial traits and diseases

Answer 24

-result from the actions of several genes working together (polygenic) andlor the combined influences of both genes and environment
-Complex or polygenic traits are not dominant or recessive. Each gene variant adds to or takes away from the actual expression of the trait (phenotype).
-Many complex traits are considered quantitative. Height is a good example because it can be measured on a numerical scale.

Question 25

regression to the mean.

Answer 25

-Extremes of a condition or trait tend to become more average over time in successive generations. For example, a very tall father tends to have sons who are shorter than he is (closer to average height), and a very short father tends to have sons who are taller than he is (again, closer to average height).

Question 26

modifier genes.

Answer 26

-Genes that contribute to the phenotype but are not the primary cause of its expression are considered modifier genes.
-For example, two children in the same family (with the same primary mutation) may have cystic fibrosis (CF), but one might be much sicker than the other. Assuming they are both receiving the same quality of care, some difference probably exists in their modifier genes. Perhaps one has a gene variant that is somewhat protective, whereas the other has a gene variant that makes things worse. Evidence of the actions of modifier genes is seen in disorders such as Gaucher disease, hemochromatosis, beta-thalassemia, and polycystic kidney disease, although not ali modifier genes involved have been identified.

Question 27

Risk alleles

Answer 27

gene variants that increase a person’s risk for developing the phenotype.

Question 28

Threshold
Figure 4-9

Answer 28

-For every trait, there is a theoretical point called the threshold, which indicates the point at which the number of risk alleles needed [Q express the disorder has just been met.
-all points to the right of the threshold line are designated as “affected.” The threshold for expression of a complex trait or health problem varies with each individual, even within one family.

Question 29

Liability model

Answer 29

-a liability model is an estimate of the risk an individual has for experiencing a complex disease based on the number of risk alleles in his or her kindred.

Question 30

Twin concordance

Answer 30

-Twin concordance can help determine how much genetic factors contribute to disease development. If twins are monozygotic (identical), they share nearly identical genomes. If one twin has a disease that is completely due to genetic variants, then the likelihood of the other twin having the same disease is nearly 100%.
- Dizygotic (fraternal) twins share only about 50% of their genomes. Most are raised together and so share much of their environment. If the incidence of a trait being shared by twins is equal for monozygotic and dizygotic twins, it is likely to have a strong environmental component and some genetic contribution.

Question 31

Heritability estimates

Answer 31

Heritability estimates (the proportion of the variance accounted for by genetic factors) tell us how important genetics is in creating disease risk.

Question 32

ecurrence risk.

Answer 32

-Families that already have one child with a genetic disorder may be concerned that future children will have the same disorder, which is known as the recurrence risk.

Question 33

genetic susceptibility

Answer 33

• a genetic susceptibility is having one or more gene variations that increase the risk for disease expression.
  -Having a specific mutation that works as a susceptibility gene only increases the risk for disease but does not (often) guaramee it.

Question 34

genetic resistance.

Answer 34

-Scientists have termed genes that can protect against the development of a specific disease resistance genes or modifier genes, which confer genetic resistance.
-Because not many such genes have been identified to date, they are largely considered “theoretical,” but few genetic professionals doubt their existence.
Figure 4-12

Question 35

Summary pt. 1

Answer 35

-Monogenic traits can be explained and shown to follow stable patterns of inheritance with strong panerns of probability prediction. For traits and health problems associated with the input of more than one gene (polygenicinput), the probability of expression is more difficult. However, the expression of even monogenic traits can be modified by other genes, the gender of the parent who transmitted the gene, interactions with the environment, and factors that have yet to be identified. Therefore, some of the Mendelian rules can be thwarted. In a sense, when we understand how these other factors interact with genetic facrors, we may be able to “beat our genes.” For example, DMT2, which is a multifactorial, complex disorder, shows a strong autosomal-dominant pattern of inheritance, although no specific single gene has been identified as causative. Environment clearly plays a role because those individuals who have the genetic risk can delay the onset of the disease for two decades (or more) by maintaining a normal weight and participating in a lifelong program of moderate-intensity exercise.

• Mendelian inheritance applies only to monogenic (single-gene) traits and disorders.
• Autosomal-dominant traits are expressed whether both alleles are dominant or only one allele is dominant.
• The genotype and phenotype for autosomal-dominant traits can be the same but do not have to be
the same.
• When a dominant allele is paired with a recessive allele, only the dominant allele is expressed.
• Having a gene mutation for a disorder does not necessarily mean that the disorder will ever develop.
• Many autosomal-dominant disorders are lethal in the person who is homozygous for that allele.
• Autosomal-recessive traits usually are only expressed in the homozygous state.
• The child of a person who expresses an autosomal-recessive trait will have at least one of the two recessive alleles and is an obligate carrier of that trait.
• The fact that autosomal-recessive alleles can go unexpressed for many generations contributes to the
survival or preservation of the trait.
• The Y chromosome is small, with less than 300 protein-encoding gene alleles.
• Only the tips of the Y chromosome have gene alleles that pair with alleles on the X chromosome.
• Y chromosome traits are all paternal in origin and transmitted only from father to son.
• Because males have only one X chromosome, they have only one allele for nearly every gene on the X chromosome.

Question 36

Summary pt. 2

Answer 36

• The X chromosome has about 1,500 genes, most of which code for non-sex-related functions.
• In females, one of the two X chromosomes in every somatic cell is inactivated to preven t a “double dose” of X chromosome alleles.
• X-linked-recessive traits and disorders are expressed more frequently in males.
• A man with an X-linked-recessive disorder transmits the allele to all daughters and to none of his sons.
• X-linked-dominant disorders are very rare, and males are more profoundly affected than females.
• Punnett square probability is less reliable with smaller numbers of offspring.
• The probability for offspring genotypes and phenotypes is calculated for each pregnancy and not for families as a whole.
• Common disorders that are considered complex, multifactorial diseases include some forms of diabetes
mellitus, atherosclerosis, obesity, and cancer.
• Complex traits and disorders are neither dominant nor recessive but represent the influence of multiple genes interacting with the environment.
• Complex traits are quantitative expressions that vary within families and within populations.
• Modifier genes are not responsible for an actual genetic feature or product but modify how the trait is expressed.
• Each person has a unique distribution of risk alleles for any complex trait.
• The threshold of expression for a complex health problem or trait varies with each individual, even within a family.
• Heritability estimates help determine how much of the expression of a complex trait is dependent on
genetic factors rather than environmental and lifestyle factors.
• When the incidence of trait concordance is higher among monozygotic twins than for dizygotic twins, genetic factors have a stronger influence than environmental factors.
• When the incidence of trait concordance among monozygotic twins is the same as among dizygotic
twins, environmental influences are at least equal to or greater than genetic factors.
• Recurrence risks are easier to calculate for monogenic traits or problems than for complex traits.

Question 37

1. How many alleles for the single gene trait of blood type (A, B, O) does a person with the normal number of chromosomes inherit from his or her biological parents?
   a. 1
   b. 2
   c. 3
   d. 0

Answer 37

B

Question 38

2. How are gene penetrance and gene expressivity different?
   A. With penetrance, the gene is either expressed completely or is not expressed at all; with expressivity, the gene is always expressed, but the degree of expression can range from minor to extreme.
   B.Penetrance and expressivity are both related to “gene dosage.” With penetrance, only one copy of the gene is expressed; with expressivity, more than one copy of the gene can be expressed.
   C. Gene penetrance and gene expressiviry are different terms for the same concept, which is the excessive expression of recessive alleles.
   D. Penetrance refers co the actual gene structure in the DNA, and expressivity refers to the chromo-some locus of the gene.

Answer 38

A

Question 39

3. Why are X-linked-recessive disorders expressed in males more frequently than in females?
   a. Hemizygous X alleles in males have homozygous expression.
   b. One X chromosome of a pair is always inactive in all female cells.
   c. Females have more effective DNA repair mechanisms than do males.
   d. Expression of genes from the Y chromosome does not occur among females.

Answer 39

A

Question 40

4. Which types of traits or health problems cannot be predicted or explained using Mendelian rules?
   a. Traits/health problems with high penetrance
   b. Y-linked-dominant traits/health problems
   c. Codorninant traits/health problems
   d. Polygenic traits/health problems

Answer 40

D

Question 41

5. Which disorder demonstrates a strong gene-environment interaction?
   a. Marfan syndrome
   b. Diabetes mellitus type 2
   c. Neurofibromatosis type 1
   d. Red-green color blindness

Answer 41

B

Question 42

6. Which statement or condition best reflects pleiotropy?
   a. A mutation in a single gene results in the expression of problems in a variety of organs.
   b. The susceptibility to a problem is an inherited trait, but the development of the problem is related to environmental conditions.
   c. A mutated gene is inherited, but the results of expression of that gene are not evident until middle
   or late adulthood.
   d. Several genes are responsible for the mechanism of hearing, and a mutation in anyone of them results in hearing impairment.

Answer 42

A

Question 43

7. Which common health problem has the lowest heritability estimate?
   a. Asthma
   b. Hypertension
   c. Pyloric stenosis
   d. Congenital heart disease

Answer 43

D

Question 44

8. Under which condition for a complex disorder is the problem more likely to recur in a family?
   a. The mother’s great-grandfather had a milder form of the problem.
   b. The problem is found in only one child in a set of dizygotic twin boys.
   c. The affected child is male, and the disorder usually occurs among females.
   d. The problem has never been seen in the family going back five generations.

Answer 44

C