Chapter 2: Genes and Genetic Diseases

Question 1

DNA, RNA, and Proteins: Heredity at the Molecular Level

Answer 1

1. Genes, the basic units of inheritance, are composed of sequences of deoxyribonucleic acid (DNA) and are located on chromosomes.
2. Each subunit of DNA, called a nucleotide, is composed of one deoxyribose, a phosphate molecule, and one of four types of nitrogenous bases. The physical structure of DNA is a double helix. The two strands connect by the nitrogenous bases, with thymine bonding
   to adenine, and guanine bonding to cytosine.
3. The four DNA bases code for amino acids, which in turn make up proteins. The amino acids are specified by triplet sets of nitrogenous bases in specific orders, called codons. Several codons correspond to the same amino acid in many cases.
4. DNA replication is based on complementary base pairing, in which a single strand of DNA serves as the template for attracting complementary bases that form a new strand of DNA.
5. DNA polymerase is the primary enzyme involved in replication. It adds bases to the new DNA strand and performs “proofreading” functions.
6. A mutation is an alteration of genetic material (e.g., base pair substitution, frameshift mutation). Substances that cause mutations are called mutagens.
7. Mutations are rare events, and the rate of mutations varies from gene to gene. Mutational hot spots are DNA sequences with particularly high mutation rates.
8. Transcription and translation, the two basic processes in which proteins are specified by DNA, both involve ribonucleic acid (RNA). RNA is chemically similar to DNA, but it is single stranded, has a ribose sugar molecule, and has uracil rather than thymine as one of its four nitrogenous bases (uracil pairs with the base adenine).
9. Transcription is the process by which a DNA template synthesizes a RNA, thus forming messenger RNA (mRNA).
10. Much of the RNA sequence is spliced from the mRNA before the mRNA leaves the nucleus. The excised sequences are called introns, and those that remain to code for proteins are called exons.
11. Translation is the process by which RNA directs the synthesis of polypeptides. This process takes place in the ribosomes, which consist of proteins and ribosomal RNA (rRNA).
12. During translation, mRNA interacts with transfer RNA (tRNA), a molecule that has an attachment site for a specific amino acid and an anticodon, a region that matches up with a 3-base codon on the mRNA. The ribosome moves along the mRNA, matching different tRNAs to codons on the mRNA, and forming a growing
    chain of amino acids called a polypetide.

Question 2

Chromosomes

Answer 2

1. Human cells consist of diploid somatic cells (body cells with 23 pairs of chromosomes, 46 total) and haploid gametes (sperm and egg cells with 23 total chromosomes).
2. Humans have 23 pairs of chromosomes. Twenty-two of these pairs are autosomes, ones that appear virtually identical (homologous) between males and females). The remaining pair consists of the sex chromosomes. Females have two homologous X chromosomes
   as their sex chromosomes; males have an X and a Y chromosome.
3. A karyogram is an ordered display of chromosomes arranged according to length and the location of the centromere. The karyogram is the visual representation of the individual’s chromosome
   karyotype.
4. Various types of stains can be used to make chromosome bands more visible. Chromosome bands can be used to identify chromosomes and identify variations.
5. About 1 in 150 live births has a major diagnosable chromosome abnormality. Chromosome abnormalities are the leading known cause of intellectual disability and miscarriage.
6. Euploid cells are ones with the normal number of chromosomes. Polyploidy is a condition in which a cell has some multiple of the normal number of chromosomes. Humans have been observed to
   have triploidy (three copies of each chromosome) and tetraploidy (four copies of each chromosome); both conditions are lethal.
7. Aneuploidy is when a cell does not have a multiple of 23 chromosomes: there is an extra or missing single chromosome. Trisomy is a type of aneuploidy in which one chromosome is present in three copies. A partial trisomy is one in which only part of a chromosome is present in three copies. Monosomy is a type of aneuploidy in which one chromosome is present in only
   one copy.
8. In general, monosomies cause more severe physical defects than do trisomies, illustrating the principle that the loss of chromosome material has more severe consequences than the duplication of chromosome material.
9. Down syndrome, a trisomy of chromosome 21, is the best-known disease caused by a chromosome aberration. It affects 1 in 800 to 1 in 1000 live births.
10. Most aneuploidies of the sex chromosomes have less severe consequences than those of the other chromosomes.
11. The most commonly observed sex chromosome aneuploidies are the 47,XXX karyotype, 45,X karyotype (Turner syndrome), 47,XXY karyotype (Klinefelter syndrome), and 47,XYY karyotype.
12. Abnormalities of chromosome structure include deletions, duplications, inversions, and translocations.

Question 3

Elements of Formal Genetics

Answer 3

1. Mendelian traits are caused by single genes, each of which occupies a position, or locus, on a chromosome.
2. Alleles are different forms of genes located at the same locus on a chromosome.
3. At any given locus in a somatic cell, an individual has two genes, one from each parent. An individual may be homozygous (alleles are identical) or heterozygous (alleles are different) for a locus.
4. An individual’s genotype is his or her genetic makeup, and the phenotype reflects the interaction of genotype and environment.
5. In a heterozygote, a dominant gene’s effects mask those of a recessive gene. The recessive gene is expressed only when it is present in two
   copies.

Question 4

Transmission of Genetic Diseases

Answer 4

1. Genetic diseases caused by single genes usually follow autosomal dominant, autosomal recessive, X-linked dominant, or X-linked recessive modes of inheritance. Pedigree charts are important tools
   in the analysis of modes of inheritance.
2. Autosomal dominant inheritance affects males and females are equally likely and the two sexes are equally likely to transmit to their offspring. Skipped generations are not seen in classic autosomal dominant pedigrees. Affected heterozygous individuals transmit the trait to approximately half their children.
3. Recurrence risks specify the probability that future offspring will inherit a genetic disease. For single-gene diseases, recurrence risks remain the same for each offspring, regardless of the number of
   affected or unaffected offspring.
4. Many genetic diseases have a delayed age of onset: symptoms are not seen until some time after birth.
5. The penetrance of a trait is the percentage of individuals with a specific genotype who also exhibit the expected phenotype. A gene that is not always expressed phenotypically is said to have incomplete penetrance.
6. Expressivity is the extent of variation in phenotype associated with a particular genotype. If the expressivity of a disease is variable, penetrance may be complete but the severity of the disease can
   vary greatly.
7. Epigenetics involves changes, such as the methylation of DNA bases, that do not alter the DNA sequence but can alter the expression of genes.
8. Genomic imprinting, which is associated with methylation, results in differing expression of a disease gene, depending on which parent
   transmitted the gene.
9. Autosomal recessive inheritance affect males are females in equal proportions. Consanguinity (mating of related individuals) is sometimes present in families with autosomal recessive diseases, and it becomes more prevalent with rarer recessive diseases. The
   disease may be seen in siblings but not their parents. The recurrence risk for autosomal recessive diseases is 25%.
10. Most commonly, biologic parents of children with autosomal recessive diseases are both heterozygous carriers of the disease gene.
11. Carrier detection tests for autosomal recessive diseases are routinely available.
12. In each normal female somatic cell, one of the two X chromosomes is inactivated early in embryonic development. X inactivation is random, fixed, and incomplete (i.e., only part of the chromosome
    is actually inactivated) and involves methylation.
13. Gender is determined embryonically by the presence of the SRY gene on the Y chromosome. Embryos that have a Y chromosome (and thus the SRY gene) become males, whereas those lacking the Y chromosome become females. When the Y chromosome lacks
    the SRY gene, an XY female can be produced. Similarly, an X chromosome that contains the SRY gene can produce an XX male.
14. Sex linked inheritance is caused by mutations in genes on sex chromosomes. X-linked genes are those that are located on the X chromosome. Nearly all known X-linked diseases are caused by X-linked recessive genes.
15. Males are hemizygous for genes on the X chromosome. If a male inherits a recessive disease gene on the X chromosome, he will be affected by the disease because the Y chromosome does not carry a normal allele to counteract the effects.
16. X-linked recessive inheritance produces traits more often in males than in females because males need only one copy of the gene to express the disease. Because a father can give a son only a Y chromosome, biologic fathers cannot pass X-linked genes to their sons.
    Skipped generations often are seen in X-linked recessive disease pedigrees because the gene can be transmitted through carrier females. The gene is passed from an affected father to his daughters, who transmit to approximately half of their sons.
17. Recurrence risks for X-linked recessive diseases depend on the carrier and affected status of the mother and father.
18. A sex-limited trait is one that occurs only in one sex (gender). A sex-influenced trait is one that occurs more often in one sex than in the other.

Question 5

Linkage Analysis and Gene Mapping

Answer 5

1. During meiosis I, crossover occurs and can cause recombinations of alleles located on the same chromosome. Loci that are located very close to one another are unlikely to experience recombination
   and are said to demonstrate linkage.
2. The major goals of the Human Genome Project were to find the locations of all human genes (the “gene map”) and to determine the entire human DNA sequence. These goals have now been accomplished and the genes responsible for approximately 5000 mendelian
   conditions have been identified.

Question 6

Multifactorial Inheritance

Answer 6

1. Traits that result from the combined effects of several loci are polygenic. When environmental factors also influence the trait, it is multifactorial.
2. Many multifactorial traits have a threshold of liability. Once the threshold of liability has been crossed, the disease may be expressed.
3. Recurrence risks are difficult to determine for multifactorial inheritance. Empirical risks, which are based on direct observation of large numbers of families, are used to estimate recurrence risks.

Question 7

Question 1

Answer 7

Which of the following statements is TRUE?

A. RNA is double stranded.
B. DNA is replicated in the cytoplasm.
C. RNA contains the same bases as DNA.
D. A mutation is an inherited alteration of DNA.

Correct Answer: D

A mutation is an inherited alteration of genetic material (i.e., DNA). DNA replication takes place in the cell nucleus, not the cytoplasm. RNA is single stranded and has uracil, which is structurally similar to thymine. Therefore, the bases are slightly different for RNA.

Question 8

Question 2

Answer 8

Which term best describes an allele with an observable effect?

A. Carrier
B. Dominant
C. Recessive
D. Homozygous

Correct Answer: B

Dominant alleles have observable effects. A carrier is an individual who has a disease gene but is phenotypically normal. Recessive alleles may be hidden and are not observable. Homozygous is when two alleles at a locus are identical. Heterozygous is when two alleles at a locus are different.