CHAPTER 2Single-Gene Inheritance

CHAPTER 2Single-Gene Inheritance

CHAPTER OUTLINE

2.2 Single-gene inheritance patterns

2.3 The chromosomal basis of single-gene inheritance patterns

2.1 Genes and chromosomes

2.5 Sex-linked single-gene inheritance patterns

2.6 Human pedigree analysis

Single-gene inheritance patterns

Chapter 2 Opener

The monastery of the father of genetics, Gregor Mendel

Figure 2-9

The seven phenotypic pairs studied by Mendel

Figure 2-10

Cross-pollination and selfing are two types of crosses

Figure 2-11

Mendel’s crosses resulted in specific phenotypic ratios

Table 2-1

Figure 2-12

A single-gene model explains Mendel’s ratios

Mendel’s explanation:

1. Existence of genes – hereditary determinants of a particulate nature.

2. Genes are in pairs – alternative phenotypes of a character or trait are determined by different forms of a single type of gene – alleles.

3. Principle of segregation – members of the gene pair separate equally into gametes.

4. Gametic content – each gamete carries only one member of each gene pair.

5. Random fertilization – union of one gamete from each parent to form the offspring

Questions about heredity answered by Mendel:

1. What is inherited?alleles of genes

2. How are they inherited?according to principles of segregation and independent assortment

3. What is the role of chance?for each individual, inheritance is determined by chance,but within a population this chance operates in a contextof strictly defined probabilities

The chromosomal basis of single-gene inheritance patterns

Figure 2-13

Stages of the asexual cell cycle

Figure 2-14

Cell division in common life cycles

Figure 2-15

Key stages of meiosis and mitosis

Box 2-1

Stages of Mitosis

Box 2-2

Stages of Meiosis

Figure 2-17

Demonstration of equal segregation within one meiocyte in the yeast S. cerevisiae

Figure 2-18

DNA molecules replicate to form identical chromatids

Figure 2-19

Nuclear division at the DNA level

Genes and chromosomes

Figure 2-2

The nuclear genome

Figure 2-3

A diploid genome visualized

Figure 2-4a

Chromosomal DNA is wrapped around histones

Figure 2-4b

Chromosomal DNA is wrapped around histones

Figure 2-5

Chromosomal condensation by supercoiling

Progressive levels of chromosome packing1. DNA winds onto nucleosome spools2. The nucleosome chain coils into a solenoid3. Solenoid forms loops, and the loops attach to a central scaffold4. Scaffold plus loops arrange themselves into a giant supercoil

Visible chromosome landmarks

Chromosome number

Highest known diploid chromosome numberIndian fern Ophioglossum reticulatum (2n = 1260)

Chromosome sizeand type

Heterochromatin and euchromatin

Feulgen stain

Heterochromatin – densely staining region (more condensed)

Euchromatin – poorly staining region (contains most of the active genes)

Centromeres

Location of satellite DNA in mouse chromosomes

Telomeres

Banding patterns

G-banding chromosomes of a human female (staining with Giemsa reagent)

Enlargement of chromosome 13

Labeling for G bands of chromosome 13

Landmarks that distinguish the chromosomes of corn

Features such as size, arm ratio, heterochromatin, number and position of thickenings, number and location of nucleolar organizers, and banding patternidentify the individual chromosomes within the set that characterizes a species

Figure 2-6

Some landmarks of tomato chromosome 2

Figure 2-7

Representative chromosomal landscapes

Figure 2-8

A specific human chromosomal landscape

Sex-linked single-gene inheritance patterns

A dioecious plant species – Osmaronia dioica

A dioecious plant species – Aruncus diocius

Model Organism: Drosophila

Model Organism Drosophila

Model Organism: Drosophila

Model Organism Drosophila

Figure 2-25

Human sex chromosomes

Figure 2-26

Red-eyed and white-eyed Drosophila

Figure 2-27

An example of X-linked inheritance

Combining probabilities

Product rule When two independent events occur with the probabilities p and q respectively, then the probability of their joint occurrence is pq.  If the word "and" is used or implied in the phrasing of a problem solution, a multiplication of independent probabilities is usually required.

Example: In test crossing a heterozygous black guinea pig (Bb x bb), let the probability of a black (Bb) offspring be p = 1/2 and of a white offspring be q = 1/2.  The combined probability of the first two offspring being white (i.e. the first offspring is white and the second offspring is white) = q x q = q2 = (1/2)2 = 1/4.

Problem: What is the probability of getting 6(Red) 6(Green) 6(Blue) when all three dice are rolled at the same time? Each dice has six sides and the probability of obtaining any one side is 1/6.  So the combined probability in the present example is 1/6 x 1/6 x 1/6 = 1/216.

Sum rule Mutually exclusive events are those in which the occurrence of any one of them excludes the occurrence of the others.  The word "or" is usually required or implied in the phrasing of problem solutions involving mutually exclusive events, signaling that an addition of probabilities is to be performed.

Example: With two dice, what is the probability of getting either two 4s or two 5s? The probability of getting two 4s is 1/6 x 1/6 = 1/36. The probability of getting two 5s is 1/6 x 1/6 = 1/36. The probability of getting two 4s or two 5s is 1/36 + 1/36 = 1/18.

Problem: What is the probability of getting two 6s and one 5 on any dice when three dice (Red, Green, Blue) are rolled at the same time? Three ways to get two 6s and one 5: 6R, 6G, 5B = 1/6 x 1/6 x 1/6 or                    + 6R, 5G, 6B = 1/6 x 1/6 x 1/6 or                    + 5R, 6G, 6B = 1/6 x 1/6 x 1/6                     = 3/216 = 1/72.

Human pedigree analysis

Pedigree Analysis

- pedigree analysis is a scrutiny of records of matings

- pedigrees use standard sets of symbols to depict family trees and lineages

- pedigrees provide concise and accurate records of families

- pedigrees are helpful in following and diagnosing heritable traits (for example, diseases and medical conditions) by describing patterns of inheritance

- pedigrees are useful in mapping (locating and isolating) genes “responsible” for certain traits

Pedigree construction

- use standard set of symbols

- one generation per row (oldest at the top)

- siblings are shown in order of birth (from left to right)

- generations are given Roman numerals (I, II, III, IV, etc)

- individuals within a generation (row) are given Arabicnumerals (1, 2, 3, 4, etc)

Figure 2-28

Pedigree symbols

Analyzing pedigrees

- trial and error: consider one pattern of inheritance at a time for each mating in the pedigree and try to find evidence against it; repeat foreach pattern of inheritance, for example, autosomal recessive or dominant, X-linked recessive or dominant, etc

- patterns of inheritance follow Mendelian rules; Mendelian ratios are rarely observed

- assumption: for rare traits unaffected people entering into a familypedigree (for example, by marriage) are considered homozygousnormal

- result: pedigrees can frequently rule out, but not necessarily prove,a certain pattern of inheritance

I

II

III

IV

Autosomal recessive

- the trait is found equally in both males and females- affected individuals usually have unaffected parents- the pattern of inheritance is often horizontal with several generations

of unaffected individuals, but then several siblings in one generationare affected

I

II

III

IV

Autosomal dominant

- the trait is found equally in both males and females- every affected individual has at least one affected parent- trait shows vertical pattern of inheritance, that is affected

males and females are observed in each generation

Figure 2-30

Pseudoachondroplasia phenotype

Figure 2-31

Inheritance of an autosomal dominant disorder

Figure 2-32

Late onset of Huntington disease

Figure 2-33a

Polydactyly

Figure 2-33b

Polydactyly

I

II

III

IV

X-linked recessive

- more males than females are affected- all the sons of an affected mother will be affected- half the sons of a carrier mother will be affected- all daughters of carrier mothers will be normal, but half will be carriers- affected males do not transmit the trait to their sons- trait often skips a generation

Figure 2-36

Inheritance of an X-linked recessive disorder

Figure 2-37a

Inheritance of hemophilia in European royalty

I

II

III

IV

X-linked dominant

- trait observed in both males and females- affected males ALWAYS transmit the trait to their daughters, but to

NONE of their sons- affected females will transmit the trait to both sons and daughters- trait does not skip generation

Figure 2-39

Inheritance of an X-linked dominant disorder

I

II

III

IV

Y-linked

- only males are affected- the trait is passed from an affected father to all of his sons

Figure 2-40

Hairy ears: a phenotype proposed to be Y linked

Sex-influenced and Sex-limited Traits Not due to X-linked genesDue to autosomal genes expression influenced by sex hormones

both parents contribute equally to offspringno notable mother-to-son or father-to-daughter patterns

example: pattern baldness – sex-influenced traitalleles B and B’B for bald B’ for nonbaldB > B’ in males, B’ > B in femalesgenotype BB --- bald in both sexesgenotype BB’ --- bald in males, nonbald in femalesgenotype B’B’ -- nonbald in both sexes

There are also traits that are sex-influenced, which means that their expression is influenced by the individual's sex. This does not imply that the gene is sex-linked. A human example is pattern baldness. The gene's expression is influenced by hormonal levels and only one copy of the baldness allele is sufficient to cause baldness in a man, whereas two copies are needed in a woman. In effect, it behaves as a dominant in males and as a recessive in females. Though half the sons of a female carrier will be affected, a heterozygous male will also pass the trait to half his sons. Thus, any trait that appears more frequently in males than females is suspect as either sex-linked or sex-influenced. If it is passed from the father or the mother to half the sons, it is likely sex-influenced. If it seems to skip a generation and the pattern is grandfather to grandson, it is likely sex-linked.

I

II

III

IV

Mitochondrial inheritance

- both males and females are affected- the trait is passed from an affected mother to all her progeny- affected males do not transmit the trait to any of their progeny