S6) Genotype, Phenotype, Inheritance

Question 1

What is a pedigree chart?

Answer 1

A pedigree is a diagram showing genetic information from a family, using standardized symbols

Question 2

State 2 purposes of a pedigree chart

Answer 2

• Determines whether the pattern of inheritance for a given trait
• Discovers whether the gene in question is located on an X or Y chromosome or an autosome

Question 3

Why is it important to establish how a trait is inherited?

State 3 reasons

Answer 3

If the pattern of inheritance can be established, it can be used to predict genetic risk in several situations, including:

• Pregnancy outcomes
• Adult-onset disorders
• Recurrence risks in future off spring

Question 4

Pedigrees use a standardised set of symbols.

How are males and females represented?

Answer 4

• Squares represent males
• Circles represent females

Question 5

Pedigrees use a standardised set of symbols.

How are affected individuals represented?

Answer 5

Individuals with the phenotype in question is represented by a filled-in symbol

Question 6

Pedigrees use a standardised set of symbols.

How are heterozygotes represented?

Answer 6

Heterozygotes, when identifiable, are indicated by a shaded dot or a half-filled symbol

Question 7

Pedigrees use a standardised set of symbols.

How are individuals represented when their sex is unknown?

Answer 7

If the sex of a person is unknown, a diamond is used

Question 8

Pedigrees use a standardised set of symbols.

How are romantic relationships represented?

Answer 8

• Parents are connected by a horizontal line
• Closely related parents (such as first cousins) are connected by a double line
• Divorced parents are connected by a horizontal line with slanted lines

Question 9

Pedigrees used a standardised set of symbols.

How are offspring represented?

Answer 9

• Offspring are connected to parents by a vertical line
• Off spring are connected by a horizontal sibship line (listed in birth order from left to right)

Question 10

Pedigrees used a standardised set of symbols.

How are twins represented?

Answer 10

• Non-identical twins are connected by two diagonal lines
• Identical twins are connected by two diagonal lines as well as a horizontal sibship line

Question 11

Pedigrees used a standardised set of symbols.

How are aborted, miscarried or stillborn offspring represented?

Answer 11

Deceased offspring are represented with a cross through their respective symbols

Question 12

Pedigrees used a standardised set of symbols.

How are deceased individuals represented?

Answer 12

Deceased individuals are represented with a diagonal line through their respective symbol

Question 13

Explain the numbering system in pedigree construction

Answer 13

• Each generation is identified by a Roman numeral (I, II, III, and so on)
• Each individual within a generation is identified by an Arabic number (1,2,3, and so on)

Question 14

What are the five basic Mendelian patterns of inheritance for traits controlled by single genes?

Answer 14

• Autosomal recessive inheritance
• Autosomal dominant inheritance
• X-linked dominant inheritance
• X-linked recessive inheritance
• Y-linked inheritance

Question 15

Identify a non-Mendelian pattern of inheritance

Answer 15

Mitochondrial inheritance - traits controlled by single genes coded for by mitochondrial genes

Question 16

Identify 3 unique features of autosomal recessive inheritance

Answer 16

• All the children of two affected (homozygous) individuals are affected
• The risk of an affected child from two heterozygote parents is 25%
• For rare traits, affected individuals have unaffected parents

Question 17

What can be expected with traits on autosomes (non-sex chrosomes)?

Answer 17

• Expressed in both males and females (affected in roughly equal numbers)
• Both the male and the female parent transmit the trait

Question 18

Identify 6 different diseases with autosomal recessive inheritance

Answer 18

• Albinism
• Cystic fibrosis
• Phenylketonuria
• Sickle cell anaemia
• Thalassemia
• Xeroderma pigmentosum

Question 19

Briefly, describe the features of the following clinical conditions:

• Albinism
• Cystic fibrosis
• Xeroderma pigmentosum

Answer 19

• Albinism: absent pigments in skin, eyes, hair
• Cystic fibrosis: mucous production that blocks the ducts of certain glands and lung passages
• Xeroderma pigmentosum: lack of DNA repair enzymes leading to UV light sensitivity and skin cancer

Question 20

Briefly, describe the features of the following clinical conditions:

• Phenylketonuria
• Sickle cell anaemia
• Thalassemia

Answer 20

• Phenylketonuria: excess accumulation of phenylaline in blood leading to mental retardation
• Sickle cell anaemia: abnormal haemoglobin leading to blood vessel blockage (crises)
• Thalassemia: improper haemoglobin production with symptoms ranging from mild to fatal

Question 21

Identify 4 unique features of autosomal dominant inheritance

Answer 21

• Most affected individuals are heterozygotes and still have an abnormal phenotype
• Unaffected individuals carry two recessive alleles
• All offspring have a 50% chance of being affected
• Every affected individual has at least one affected parent

Question 22

How can one differentiate between homozygous and heterozygous patients for autosomal dominant disorders?

Answer 22

• Phenotype in homozygous dominant individuals is often more severe
• Homozygous dominant trait is often not compatible with life

Question 23

An individual with an autosomal dominant disorder has two unaffected parents. How did this disorder occur?

Answer 23

• A mutation occured in single gene
• Common for genes with high mutation rates

Question 24

Identify 4 different diseases with autosomal dominant inheritance

Answer 24

• Achondroplasia
• Ehlers-Danlos syndrome
• Marfan syndrome
• Huntington disease

Question 25

Briefly, describe the features of the following clinical conditions: - Achondroplasia - Marfan's syndrome

Answer 25

- **Achondroplasia**: dwarfism associated with defects in growth regions of long bones - **Marfan syndrome:** connective tissue defect due to mutation in fibrillin gene, individuals are incredible tall & lanky

Question 26

Briefly, describe the features of the following clinical conditions: - Ehler-Danlos syndrome - Huntington's disease

Answer 26

- **Ehlers-Danlos syndrome:** connective tissue disorder presenting with elastic skin and loose joints - **Huntington disease:** progressive degeneration of nervous system, resulting in dementia and early death

Question 27

What is sex-linked inheritance?

Answer 27

- **Sex chromsomes** are the X and Y chromosomes - Genes on the X chromosome are called **X-linked** - Genes on the Y chromosome are called **Y-linked**

Question 28

Describe paternal inheritance - genes on the Y chromosome

Answer 28

- Only males have Y chromosomes, hence, traits encoded by Y genes are passed directly from father ⇒ son - All Y-linked traits should be expressed because males are **hemizygous** for all genes on the Y chromosome

Question 29

What does it mean to be hemizygous for genes on sex chromosomes?

Answer 29

- Males cannot be homozygous or heterozygous for both X-linked and Y-linked geness - A gene present on either the X/Y chromosome is expressed in males in both the recessive and dominant forms

Question 30

Identify 3 unique features of X-linked dominant inheritance

Answer 30

- Affected males transmit the trait to all their daughters but none of their sons. - An affected heterozygous female will transmit the trait to half of her children (both genders affected equally) - On average, twice as many females are affected as males (females can be heterozygous or homozygous)

Question 31

Identify 4 unique features of X-linked recessive inheritance

Answer 31

- Affected individuals are hemizygous males and females homozygous for the recessive allele - Affected males transmit the trait to all their daughters only - Daughters of affected males are usually heterozygous (unaffected) - Sons of heterozygous females have a 50% chance of receiving the recessive gene

Question 32

Why are far more males affected by X-linked recessive genetic disorders than are females?

Answer 32

- Females have two X chromosomes and, hence, can be heterozygous or homozygous for any X-linked genes - Males only carry only one copy of the X chromosome hence are **hemizygous** for X-linked genes - Males **have no dominant X allele to mask expression** of the recessive X allele

Question 33

Identify 3 unique features of maternal mitochondrial inheritance

Answer 33

- All the children of affected females are affected - Affected females transmit the trait to all their offspring - Affected males do not transmit the trait to offspring

Question 34

Why do mitochondrial genes follow a maternal inheritance?

Answer 34

- Mitochondria are transmitted from mothers to all their children through the cytoplasm of the egg - Sperm do not contribute mitochondria at fertilization

Question 35

Outline the effects of mitochondrial disorder

Answer 35

- Mutations in mitochondrial genes reduce the amount of energy available for cellular functions - Phenotypic effects are highly variable and generally affect tissues with the highest energy demands (muscles & nervous system)

Question 36

What is the name given to mitochondrial disorders which affect mainly muscles?

Answer 36

Mitochondrial myopathies

Question 37

What is the name given to mitochondrial disorders which affect both muscles and the nervous system?

Answer 37

Mitochondrial encephalomyopathies

Question 38

Incomplete dominance does not follow predicted ratios for a Mendelian trait. Illustrate this using an example

Answer 38

**- Incomplete dominance** is the expression of a phenotype that is intermediate to those of the parents - This involves a distinctive phenotype in heterozygotes:

Question 39

Codominance does not violate the expectations of Mendel’s laws. What is this phenomenon?

Answer 39

- **Codominance** is when both alleles in a heterozygote are fully expressed - The expected Mendelian genotypic ratio of 1:2:1 is observed

Question 40

Explain the phenomenon of multiple alleles

Answer 40

- Many genes have more than two alleles (**multiple alleles**) - An individual can carry only two alleles of a gene but members of a population can carry many different alleles of a gene * E.g. blood groups*

Question 41

Explain the phenomenon of epistasis

Answer 41

- **Epistasis** is the interaction of two or more non-allelic genes to control a single phenotype - The action of one gene masks or prevents the expression of another gene *e.g. Bombay phenotype*

Question 42

What is the Bombay phenotype?

Answer 42

- The **Bombay phenotype** is when a mutation in a the h gene prevents the expression of the A and B phenotypes - Individuals homozygous for a recessive allele **h** are blocked from expressing the A or B surface antigen - They are phenotypically blood type O, even though genotypically carry I^A / I^B alleles

Question 43

Explain mendelian inheritance by independent assortment

Answer 43

- The inheritance of two traits in humans follows the principle of independent assortment - Gametes independently assort themselves during metaphase of meiosis increasing the variation in offspring

Question 44

What is a proband?

Answer 44

A **proband** is the first affected family member who seeks medical attention for a genetic disorder (indicated by an arrow)