S6) Genotype, Phenotype, Inheritance Flashcards
What is a pedigree chart?
A pedigree is a diagram showing genetic information from a family, using standardized symbols
State 2 purposes of a pedigree chart
- 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
Why is it important to establish how a trait is inherited?
State 3 reasons
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
Pedigrees use a standardised set of symbols.
How are males and females represented?
- Squares represent males
- Circles represent females
Pedigrees use a standardised set of symbols.
How are affected individuals represented?
Individuals with the phenotype in question is represented by a filled-in symbol
Pedigrees use a standardised set of symbols.
How are heterozygotes represented?
Heterozygotes, when identifiable, are indicated by a shaded dot or a half-filled symbol
Pedigrees use a standardised set of symbols.
How are individuals represented when their sex is unknown?
If the sex of a person is unknown, a diamond is used
Pedigrees use a standardised set of symbols.
How are romantic relationships represented?
- 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
Pedigrees used a standardised set of symbols.
How are offspring represented?
- 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)
Pedigrees used a standardised set of symbols.
How are twins represented?
- Non-identical twins are connected by two diagonal lines
- Identical twins are connected by two diagonal lines as well as a horizontal sibship line
Pedigrees used a standardised set of symbols.
How are aborted, miscarried or stillborn offspring represented?
Deceased offspring are represented with a cross through their respective symbols
Pedigrees used a standardised set of symbols.
How are deceased individuals represented?
Deceased individuals are represented with a diagonal line through their respective symbol
Explain the numbering system in pedigree construction
- 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)
What are the five basic Mendelian patterns of inheritance for traits controlled by single genes?
- Autosomal recessive inheritance
- Autosomal dominant inheritance
- X-linked dominant inheritance
- X-linked recessive inheritance
- Y-linked inheritance
Identify a non-Mendelian pattern of inheritance
Mitochondrial inheritance - traits controlled by single genes coded for by mitochondrial genes
Identify 3 unique features of autosomal recessive inheritance
- 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
What can be expected with traits on autosomes (non-sex chrosomes)?
- Expressed in both males and females (affected in roughly equal numbers)
- Both the male and the female parent transmit the trait
Identify 6 different diseases with autosomal recessive inheritance
- Albinism
- Cystic fibrosis
- Phenylketonuria
- Sickle cell anaemia
- Thalassemia
- Xeroderma pigmentosum
Briefly, describe the features of the following clinical conditions:
- Albinism
- Cystic fibrosis
- Xeroderma pigmentosum
- 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
Briefly, describe the features of the following clinical conditions:
- Phenylketonuria
- Sickle cell anaemia
- Thalassemia
- 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
Identify 4 unique features of autosomal dominant inheritance
- 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
How can one differentiate between homozygous and heterozygous patients for autosomal dominant disorders?
- Phenotype in homozygous dominant individuals is often more severe
- Homozygous dominant trait is often not compatible with life
An individual with an autosomal dominant disorder has two unaffected parents. How did this disorder occur?
- A mutation occured in single gene
- Common for genes with high mutation rates
Identify 4 different diseases with autosomal dominant inheritance
- Achondroplasia
- Ehlers-Danlos syndrome
- Marfan syndrome
- Huntington disease
Briefly, describe the features of the following clinical conditions:
- Achondroplasia
- Marfan’s syndrome
- 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
Briefly, describe the features of the following clinical conditions:
- Ehler-Danlos syndrome
- Huntington’s disease
- 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
What is sex-linked inheritance?
- 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
Describe paternal inheritance - genes on the Y chromosome
- 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
What does it mean to be hemizygous for genes on sex chromosomes?
- 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
Identify 3 unique features of X-linked dominant inheritance
- 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)
Identify 4 unique features of X-linked recessive inheritance
- 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
Why are far more males affected by X-linked recessive genetic disorders than are females?
- 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
Identify 3 unique features of maternal mitochondrial inheritance
- 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
Why do mitochondrial genes follow a maternal inheritance?
- Mitochondria are transmitted from mothers to all their children through the cytoplasm of the egg
- Sperm do not contribute mitochondria at fertilization
Outline the effects of mitochondrial disorder
- 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)
What is the name given to mitochondrial disorders which affect mainly muscles?
Mitochondrial myopathies
What is the name given to mitochondrial disorders which affect both muscles and the nervous system?
Mitochondrial encephalomyopathies
Incomplete dominance does not follow predicted ratios for a Mendelian trait.
Illustrate this using an example
- Incomplete dominance is the expression of a phenotype that is intermediate to those of the parents
- This involves a distinctive phenotype in heterozygotes:
Codominance does not violate the expectations of Mendel’s laws.
What is this phenomenon?
- Codominance is when both alleles in a heterozygote are fully expressed
- The expected Mendelian genotypic ratio of 1:2:1 is observed
Explain the phenomenon of multiple alleles
- 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*
Explain the phenomenon of epistasis
- 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
What is the Bombay phenotype?
- 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 IA / IB alleles
Explain mendelian inheritance by independent assortment
- 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
What is a proband?
A proband is the first affected family member who seeks medical attention for a genetic disorder (indicated by an arrow)
