Ch. 6 Pedigree Analysis, Applications, and Genetic Testing

What percentage of genes do monozygotic twins typically have in common?

100%

Tay-Sachs disease is a disorder not tested for in newborn screening programs. What is a major reason for not including Tay-Sachs disease among disorders tested in newborn screening programs?

Early detection does not allow for an effective treatment for this disorder. There is no treatment for Tay-Sachs disease currently available, so newborn screening is of no significant value.

Genetic counseling

Educational process that helps patients and family members deal with many aspects of having a genetic condition.

What is the method of detection for 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.

Sickle-cell anemia

Fetal blood sampling* or 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

What features of a pedigree would distinguish between a Y-linked trait and a trait that is rare, autosomal dominant, and sex-limited to males?

If the trait were Y-linked, an affected male would pass it on to all his sons. If the trait were autosomal and sex-limited, affected heterozygous males would pass it on to only half of their sons on average.

What individuals metabolize warfarin at a much lower rate, requiring a lower dose?

Individuals who are homozygous or heterozygous for the CYP2CP9*2 or CYP2CP9*3 alleles. If given the usual dose of warfarin, people with these genotypes are at greater risk of bleeding.

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

For a medical disorder, the concordance rate for monozygotic twins is about 55%, while it is 6% for dizygotic twins. What is the most reasonable conclusion that can be made from the data provided?

It is caused by significant environmental factors and genetic factors. The difference in concordance values indicates that there is some genetic basis, while the monozygotic value of 55%, which is less than 100%, indicates a significant amount of environmental basis also.

What can be concluded about a trait that shows a concordance of 100% in monozygotic twins and 50% in dizygotic twins?

It is caused exclusively or almost exclusively by genetic factors. Higher concordance for monozygotic twins than for dizygotic twins indicates that genetic factors play a role in determining differences in a trait.

When might you see an autosomal dominant trait skip generations?

It might skip generations when a new mutation arises or the trait has incomplete penetrance.

maternal blood screening tests

Method of screening for genetic conditions in a fetus by examining levels of certain substances in the blood of the mother. For example, the level of α-fetoprotein in maternal blood provides information about the probability that a fetus has a neural-tube defect.

Why are monozygotic twins genetically identical, whereas dizygotic twins share only 50% of their genes on average? Monozygotic twins tend to look more similar. Monozygotic twins develop from two different eggs fertilized by the same sperm, whereas dizygotic twins develop from two eggs fertilized by two different sperm. Monozygotic twins develop from a single egg fertilized by one sperm, whereas dizygotic twins develop from a single egg fertilized by two different sperm. Monozygotic twins develop from a single egg fertilized by a single sperm, whereas dizygotic twins develop from two eggs fertilized by two different sperm.

Monozygotic twins develop from a single egg fertilized by a single sperm, whereas dizygotic twins develop from two eggs fertilized by two different sperm.

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

dizygotic twins

Nonidentical twins that arise when two different eggs are fertilized by two different sperm; also called fraternal twins.

Characteristics of Y-linked traits

Only males are affected. Passed from father to all sons. Does not skip generations.

How does preimplantation genetic diagnosis differ from prenatal genetic testing?

Preimplantation genetic diagnosis determines the presence of disease-causing genes in an embryo at an early stage, before it is implanted in the uterus and initiates pregnancy. Prenatal genetic testing determines the presence of disease-causing genes or chromosomes in a developing fetus.

amniocentesis

Prenatal testing of fetal tissue that involves obtaining a sample of amniotic fluid from the uterus of a pregnant woman.

ultrasonography

Procedure for visualizing a fetus in which high-frequency sound is beamed into the uterus; sound waves that encounter dense tissue bounce back and are transformed into a picture of the fetus.

Chorionic villus sampling (CVS)

Procedure used for prenatal genetic testing in which a small piece of the chorion (the outer layer of the placenta) is removed from a pregnant woman. A catheter is inserted through the vagina and cervix into the uterus; suction is then applied to remove the sample.

Genetic Information Nondiscrimination Act (GINA)

U.S. law prohibiting health insurers from using genetic information to make decisions about health-insurance coverage and rates; prevents employers from using genetic information in employment decisions, and prevents health insurers and employers from asking or requiring a person to take a genetic test.

osteogenesis imperfecta

Ultrasound or X-ray (brittle bones)

dwarfism

Ultrasound or X-ray; some forms can be detected by DNA analysis of cells obtained by amniocentesis or chorionic villus sampling

Characteristics of autosomal recessive traits

Usually appears in both sexes with equal frequency. Tends to skip generations. Affected offspring are usually born to unaffected parents. When both parents are heterozygous, approximately one-fourth of the offspring will be affected. Appears more frequently among the children of consanguineous marriages.

Within a pedigree, a trait occurs in 11 females and only 3 males. All affected individuals have at least one affected parent. All of the daughters and none of the sons of affected males show the phenotype. What is the most likely mode of inheritance, assuming that the trait is rare and shows complete penetrance?

X-linked dominant About twice as many affected females should be present as males in such pedigrees, and affected fathers pass the trait to all their daughters but none of their sons.

Consider the list. both sexes are usually affected, but often more females than males are affected affected fathers will pass the trait onto all their daughters affected mothers will pass the trait onto half of their sons and half of their daughters does not skip generations Which of the inheritance patterns best fits the pedigree characteristics described in the list?

X-linked recessive

Consider the list. pattern shows sex bias with more affected males than females affected sons are usually born to unaffected mothers tends to skip a generation never passes from father to son all daughters of affected fathers are carriers Which of the inheritance patterns best fits the pedigree characteristics described in the list?

X-linked recessive trait

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.

A male affected with an X-linked dominant trait will have what proportion of offspring affected with the trait? 1/2 sons and 1/2 daughters all sons and no daughters all daughters and no sons 3/4 daughters and 1/4 sons

all daughters and no sons

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

appear only when both parents carry a copy of the gene for the trait, which is more likely when the parents are related.

Consider the list. usually appears in both sexes with equal frequency both parents can transmit the trait to their offspring affected offspring most commonly have an affected parent unaffected parents do not transmit the trait does not skip generations Which of the inheritance patterns best fits the pedigree characteristics described in the list?

autosomal dominant

family hypercholesterolemia

autosomal dominant trait Blood cholesterol is greatly elevated. Defect in LDL receptor. (Usually, an LDL particle attaches to an LDL receptor on the cell surface and moves into the cell, where it is broken down and released for use by the cell.)

Within a pedigree that includes three generations and various groups of siblings and cousins, a trait of interest appears only in two individuals, who are brother and sister. Assuming complete penetrance, what is the most likely mode of inheritance?

autosomal recessive

Which was the most important consideration in choosing genetic conditions for mandatory newborn screening?

availability of effective treatments and early interventions Early identification is only crucial when an early treatment is available to prevent or reduce symptoms.

What produces lower-than-normal levels of α-fetoprotein?

chromosomal abnormalities

How might genetic testing lead to genetic discrimination?

employment and health insurance

Which feature of human biology and culture makes the study of human genetics difficult? knowledge of human anatomy, physiology, and biochemistry. family size family records number of genetically influenced traits available for study

family size

monozygotic twins

identical twins formed when one zygote splits into two separate masses of cells, each of which develops into a separate embryo

consanguinity

mating between closely related people

heterozygote screening

members of a population are tested to identify heterozygous carriers of recessive disease-causing alleles—people who are healthy but have the potential to produce children with a particular disease.

Traditionally, genetic counselors have helped families to reach their own decisions about reproductive and medical choices by providing

nondirected counseling. Traditionally, genetic counselors have been trained to apply nondirected counseling, meaning that they provide information and facilitate discussion but do not bring their own opinions and values into the discussion.

pedigree

often used to study human inheritance Pictorial representation of a family history, essentially a family tree that outlines the inheritance of one or more characteristics. Often contain variety of genetic parameters including measures of relatedness, inbreeding coefficients, genotype predictions, genetic risk values, and estimates of linkage among genes

Y-linked traits

only appear in males and all male offspring of an affected male are affected

A ________________ is a pictorial representation of a family history that outlines the inheritance of specific characteristics.

pedigree

Amniocentesis and chorionic villus sampling are often used in _____ genetic testing.

prenatal Prenatal genetic tests are those that are conducted before birth and now include procedures for diagnosing several hundred genetic diseases and disorders.

newborn screening

testing for genetic disorders in newborn infants

presymptomatic genetic testing

testing of healthy adults for genes that might predispose them to a genetic condition in the future

concordance

the percentage of twin pairs that are concordant for a trait

proband

the person from whom the pedigree is initiated

concordant trait

the trait shared by both members of a twin pair

obligate carriers

those who have an affected parent and affected children and therefore must themselves carry the mutation

The interpretation of genetic tests can be complicated by all of these EXCEPT traits skipping generations. the influence of environmental factors. the presence of numerous causative mutations. incomplete penetrance.

traits skipping generations.

What is the method of detection for cleft lip and palate?

ultrasound

Genetic discrimination and policy

1970s: African Americans carrying sickle-cell trait had difficulty finding employment and health insurance Genetic Information Nondiscrimination Act (GINA) passed recently in 2008... but only addresses health care not life insurance, and the future of this law is uncertain. Is your DNA private or is it like a fingerprint? Direct to Consumer genetic testing was allowed by the FDA beginning in April 2017. In vitro fertilization (IVF) for preimplantation genetic testing is now typically covered by health insurance... Louise Brown, born in 1978, was the first "test tube baby" born using in vitro fertilization (IVF). When it was first carried out, many people felt that it was a threat to humanity. In 2010, a Nobel Prize was awarded to Dr. Edwards for developing IVF. By 2012, IVF had led to the birth of an estimated five million babies worldwide. Early in its design, IVF was not regulated to any great degree by the government. Would we do anything different? In 2018 gene-edited babies were created, the doctor responsible received a 3-yr prison term

What are some common reasons people seek genetic counseling?

A person knows of a genetic disease in the family. A couple has given birth to a child with a genetic disease, birth defect, or chromosome abnormality. A couple has a child who is intellectually disabled or has a close relative who is intellectually disabled. 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. Husband and wife are closely related (e.g., first cousins). A couple experiences difficulties achieving a successful pregnancy. A pregnant woman is concerned about exposure to an environmental substance (drug, chemical, or virus) that causes birth defects. A couple needs assistance in interpreting the results of a prenatal or other test. 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.

How are adoption studies used to separate the effects of genes and the environment in the study of human characteristics? Adoption studies assume that the environments of biological and adoptive families are independent. Adoption agencies carefully select a family that resembles the adoptee's biological family. Adoptees and their biological mothers share the same environment during prenatal development. Adoption studies assume that the environments of biological and adoptive families are more alike than would be expected by chance.

Adoption studies assume that the environments of biological and adoptive families are independent. Having independent environments is important when making the distinction between genes and the environment.

What assumptions underlie the use of adoption studies in genetics? Adoptees have no contact with their biological parents after birth. The adoptive parents and biological parents are not related. The environments of biological and adoptive parents are independent. All of the above are correct.

All of the above are correct.

The tendencies of autosomal dominant traits

Autosomal dominant traits tend to appear equally in males and females. Unaffected people do not transmit the trait and affected people have at least one affected parent.

Consider the list. affected offspring are usually born to unaffected parents usually appears in both sexes with equal frequency tends to skip a generation appears more frequently among the children of consanguine (first cousin) marriages Which of the inheritance patterns best fits the pedigree characteristics described in the list?

Autosomal recessive

The tendencies of autosomal recessive traits

Autosomal recessive traits usually appear equally in males and females and tend to skip generations. They are more likely to appear among progeny of related parents.

Lesch-Nyhan syndrome

Biochemical tests on cells obtained by amniocentesis or chorionic villus sampling

Tay-Sachs disease

Biochemical tests on cells obtained by amniocentesis or chorionic villus sampling

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? Genetic factors are extremely important. Genetic factors are somewhat important. Genetic factors are unimportant. Both genetic and environment factors are important.

Both genetic and environment factors are important.

Characteristics of X-linked dominant traits

Both males and females are usually affected; often, more females than males are affected. Does not skip generations. Affected sons must have an affected mother; affected daughters must have either an affected mother or an affected father. Affected fathers pass the trait to all their daughters. Affected mothers (if heterozygous) pass the trait to half of their sons and half of their daughters.

genetic mosaics (chimeras)

Condition in which regions of tissue within a single individual have different chromosome constitutions. an arise from a number of different processes. Often, somatic mutations or errors in the separation of chromosomes during early development lead to genetically distinct groups of cells within the body. There can also be exchanges of cells and DNA between twins or between mother and child during pregnancy. Mosaicism was once thought to be rare, but the increasing use of DNA sequencing has revealed that it may be common. For example, in 2012, researchers sequenced skin cells and discovered that 30% of the cells contained genetic variants called copy-number variations. Another study examined CNVs in diverse tissues from six people and also found major differences in CNVs, even within a single person.

What some special features of mating within humans?

Controlled mating not possible Long generation time Small family size

Phenylketonuria

DNA analysis of cells obtained by amniocentesis or chorionic villus sampling

What is the method of detection for cystic fibrosis?

DNA analysis of cells obtained by amniocentesis or chorionic villus sampling

_____ twins are often called "fraternal" and share, on average, 50% of their alleles.

Dizygotic Dizygotic (nonidentical) twins arise when two separate eggs are fertilized by two different sperm, producing genetically distinct zygotes and share, on average, only 50% of their genes.

_____ twins result when two separate eggs are fertilized by two different sperm.

Dizygotic Dizygotic (nonidentical) twins arise when two separate eggs are fertilized by two different sperm, producing genetically distinct zygotes.

X-linked dominant traits

Do not skip generations Affected males pass the trait on to all their daughters and none of their sons. Affected females (if heterozygous) pass the trait on to about half of their sons and about half of their daughters.

X-linked recessive traits

First, these traits appear more frequently in males than in females because males need inherit only a single copy of the allele to display the trait, whereas females must inherit two copies of the allele, one from each parent, to be affected. Second, because a male inherits his X chromosome from his mother, affected males are usually born to unaffected mothers who carry an allele for the trait. Because the trait is passed from unaffected female to affected male to unaffected female, it tends to skip generations. When a woman is heterozygous, approximately half of her sons will be affected and half of her daughters will be unaffected carriers. They are not passed from father to son, because a son inherits his father's Y chromosome, not his X. In Figure 6.7, there is no case in which both a father and his son are affected. All daughters of an affected man, however, will be carriers (if their mother is homozygous for the normal allele). When a woman displays an X-linked recessive trait, she must be homozygous for the trait, and all her sons will also display the trait.

The _____ of 2008 prohibits health insurers from using genetic information to make decisions about health insurance coverage and rates, and employers from using genetic information in employment decisions.

Genetic Information Nondiscrimination Act The Genetic Information Nondiscrimination Act prohibits health insurers from using genetic information to make decisions about health insurance.

A trait exhibits 100% concordance for both monozygotic and dizygotic twins. What conclusion can you draw about the role of genetic factors in determining differences in the trait?

Genetic factors are unimportant. The fact that dizygotic twins have 100% concordance while only sharing 50% of the same genes indicates that genetic factors are not important.

noninvasive prenatal screening (NIPS)

Genetic test performed on a fetus without taking a tissue sample from the fetus; usually performed by testing fetal DNA found within the maternal blood.

preimplantation genetic diagnosis (PGD)

Genetic testing on an embryo combined with in vitro fertilization to allow the implantation of embryos that are free of a specific genetic defect.

Why are humans both the best and worst organisms to study?

Humans are both the best and the worst of all organisms for genetic study. On the one hand, we know more about human anatomy, physiology, and biochemistry than about that of most other organisms, so many well-characterized traits are available for study. Families often keep detailed records about their members extending back many generations. Furthermore, a number of important human diseases have a genetic component, so the incentive for understanding human inheritance is tremendous. On the other hand, the study of human genetic characteristics presents some major challenges. First, controlled matings are not possible. With other organisms, geneticists carry out specific crosses to test their hypotheses about inheritance. We have seen, for example, that the testcross provides a convenient way to determine whether an individual with a dominant trait is homozygous or heterozygous. Unfortunately (for the geneticist at least), matings between humans are usually determined by romance, family expectations, or—occasionally—accident rather than by the requirements of science. Another challenge is that humans have a long generation time. Human reproductive age is not normally reached until 10 to 14 years after birth, and most people do not reproduce until they are 18 years of age or older; thus, generation time in humans is usually about 20 years. This long generation time means that even if geneticists could control human crosses, they would have to wait an average of 40 years just to observe the F2 progeny. In contrast, generation time in Drosophila is 2 weeks; in bacteria, it's a mere 20 minutes. Finally, human family size is generally small. Observation of even the simple genetic ratios that we learned in Chapter 3 would require a substantial number of progeny in each family. When parents produce only 2 children, the detection of a 3 : 1 ratio is impossible. Even an extremely large family of 10 to 15 children would not permit the recognition of a dihybrid 9 : 3 : 3 : 1 ratio. Although these special constraints make genetic studies of humans more complex, understanding human heredity is tremendously important. Therefore, geneticists have been forced to develop techniques that are uniquely suited to human biology and culture.

direct-to-consumer genetic tests

Test for a genetic condition that can be purchased directly by a consumer without the involvement of a physician or an other health-care provider.

karyotype

The complete set of chromosomes possessed by an organism; usually presented as a picture of a complete set of its metaphase chromosomes.

Which of these is one of the assumptions that underline the use of adoption studies in genetics? The environments of the biological and adoptive parents are independent. The adoptive parents and the biological parents share at least one pair of grandparents. The trait being studied is likely inherited as an autosomal recessive condition. Adopted children continue to have some interaction with their biological parents after their adoption.

The environments of the biological and adoptive parents are independent. Adoption studies assume that the environments of biological and adoptive families are independent.

What typically happens when a fetus has a neural-tube defect?

The level of α-fetoprotein is significantly higher than normal. The level of α-fetoprotein is significantly higher than normal when the fetus has a neural-tube defect or one of several other disorders.