Transmission Genetics Flashcards
1
Q
What were the 3 theories of inheritance?
A
- Pangenesis: skills and traits of parents are transferred to the gonads and then passed onto offspring
- Homunculus: sperm contains all genetic material from the man and it implants in woman who incubates only
- Mendelian Inheritance: organisms have two copies of a particle that controls phenotype and is inherited
2
Q
What is the 1st Law of Mendelian Inheritance:
A
- Law of segregation
- The two alleles (and chromosomes) segregate from each other into gametes
- Each gamete has 1/2 chance of inheriting each allele
- Gametes combine randomly to form the next generation
3
Q
What is a test cross?
A
Crossing an organism with a homozygous recessive to determine its genotype
4
Q
What is the F2 ratio for autosomal recessive inheritance of 1 trait?
A
Genotype:
1 homozgous dominant: 2 heterozgyotes: 1 homozygous recessive
Phenotype:
3 dominant: 1 recessive
5
Q
What is Mendel’s 2nd Law?
A
- Law of Independent assortment
- Each pair of alleles (and chromosomes) segregates independently of all other alleles during gamete formation
6
Q
Describe the general pattern of a autosomal recessive dihybrid cross:
A
P: Homo dom x homo rec
F1: Double heterozygote
F2: 9:3:3:1
7
Q
What are the distinguishing features of autosomal recessive inheritance in human pedigrees?
A
- Affects males and females equally
- The trait can ‘skip’ generations
- Two unaffected parents can have an affected child
e. g. CF, albinism, Tay-Sachs
8
Q
What are the distinguishing features of autosomal dominant inheritance in human pedigrees?
A
- Affects males and females equally
- Transmission from both sexes to both sexes
- All affected children must have an affected parent
- The trait does not skip generations
e. g. Achondroplasia, Huntington disease
9
Q
What is a reciprocal cross?
A
- Tests the role of parental sex on inheritance patterns
- Female of strain 1 is crossed with male of strain 2 and then female of strain 2 is crossed with male of strain 1
10
Q
What are the distinguishing features of X-linked recessive inheritance in human pedigrees?
A
- Males usually affected
- The presence of female carriers
- No male to male transmission
e. g. Haemophilia, RG colour blindness
11
Q
What are the distinguishing features of X-linked dominant inheritance in human pedigrees?
A
- Both sexes affected byt often an excess of females
- Females usually less severely affected (X-inactivation)
- No male to male transmission
E.g. Rett syndrome, incontinetia pigmenti
12
Q
What is Mendel’s chromosome theory? How is it supported?
A
- The theory is that genes are on chromosomes
Supported by: - Behaviour of chromosomes at meiosis- parallels Mendel’s laws (segregations and independent assortment)
- Inheritance of certain traits follow the inheritance of particular chromosomes e.g. X-linked genes
13
Q
What are the single gene extensions to Mendelian Inheritance?
A
- Other types of dominance (incomplete and codominance)
- Multiple alleles (3 or more)
- Lethal alleles
- Penetrance and expressivity
- Effect of environment
- Sex influenced and sex limited traits
14
Q
What are the 3 types of dominance?
A
- Complete: the heterozygote shows the phenotype of the dominant phenotype
- Incomplete: the heterozygote shows a phenotype that is a blend of the two homozygotes e.g. white x purple = pink
- Codominance: both alternative traits are expressed in the heterozgyote- neither phenotype is dominant e.g. AB blood groups
15
Q
Do variations in dominance negate Mendel’s laws of segregation?
A
- No, they reflect differences in the way gene products control the production of phenotypes
16
Q
What are lethal alleles?
A
- These alleles have the potential to cause the death of an organism if the organism is homozgyous recessive for the mutation
e.g. Yellow coat colour in mice:
Ay = yellow
A = agouti
Cross:
Ay A (yellow) x Ay A (yellow)
Offspring ratio:
2 Yellow (Ay A): 1 agouti (A A) - Explanation the Ay allele is dominant for coat colour but recessive for lethality (pleiotropic gene)
- Offspring were 1 Ay Ay (dead): 2 Ay A (yellow) and 1 A A (agouti)
17
Q
What is penetrance?
A
- The proportion of individuals with the genotype that exhibit the expected genotype
- Measured at the population level (within an individual it is just penetrant or not)
E.g. dominant disorder retinoblastoma shows 80% penetrance. 80% of people with disease mutation will develop tumours.
18
Q
What is expressivity?
A
- The degree of expression of severity of phenotype in an individual with the genotype
e. g. one retinal tumour vs multiple retinal tumours
e. g. polydactyly: one extra finger on on hand vs many extra digits on hands and feet
19
Q
How are alleles affected by the environment?
A
- Many alleles are affected in how/if they are expressed phenotypically by the environment e.g. temperature, diet etc.
e. g. Coat colour in Arctic Foxes: during winter it is white, in summer it is brown (protein is temperature sensitive)
e. g. PKU- if phenylalanine is absent from diet there are no symptoms
20
Q
What are sex influenced traits?
A
- These are traits in which gender governs the inheritance pattern
e. g. an allele can be dominant in one sex but recessive in the other
e. g. pattern baldness: dominant in males, recessive in females
21
Q
What are sex limited traits?
A
- Certain traits that are only expressed in one gender
e. g. cock-feathering: recessive allele only expressed in males
22
Q
What is a heterogenous trait?
A
- A trait that is controlled by multiple genes
- A mutation of more than 1 gene can produce exactly the same phenotype
e. g. deafness in humans - We can test if mutations are in the same gene or different genes using a compementation test
23
Q
What is a complementation test?
A
When organisms homozygous for mutations that show the same phenotype but are in different genes when they are crossed together the progeny are wild-type. The mutations complement one another.
When organisms homozygous for mutations that show the same phenotype and are in the same gene are crossed together then the progeny are mutant. They fail to complement.
24
Q
What are the 5 gene interactions that can affect Mendelian ratios?
A
- Novel phenotypes arising from combined gene action (9:3:3:1)
- Complementary gene action (9:7)
- Epistasis (Recessive: 9:3:4, Dominant 12:3:1)
- Suppression (13:3)
- Duplicate genes (15:1)
25
How do novel phenotypes arise from combined gene action?
- When two genes control the same trait, often in parallel pathways
- The double homozgyous mutant produces a novel phenotype
e.g. Colour in snakes:
P1/2: Pure breeding orange (aaBB) x Pure breeding black (AAbb)
F1: All wildtype (AaBb)
F2: 9 wildtype (A-B-): 3 orange (aaB-), 3 black (A-bb) and 1 albino (aabb)
26
How does complementary gene action occur?
- Also called duplicate recessive epistasis
- Distinguished by a 9:7 F2 dihybrid ratio
- Occurs when two genes control a trait in a pathway, and you need a dominant allele for both genes to produce the dominant phenotype
e.g. Colour in corn flowers:
- controlled by two genes:
Colourless precursor 1 -Gene C-> colourless precursor 2 -Gene P-> Purple pigment
- When two purple double heterozygotes (CcPp) are crossed to produce F2:
9 purple (C-P-): 7 white (C-pp), (ccP-) (ccpp)
27
What is epistasis?
- Phenotype produced by a mutant allele (the epistatic allele blocks or masks the phenotype produced by alleles of another gene
- No new phenotypes are produced, but fewer than 4 phenotypes expected with a cross of 2 genes
- Usually occurs because the genes are acting in the same pathway for producing the traits
28
What is recessive epistasis?
- A recessive epistatic allele blocks/masks the phenotypic effects of other alleles only when it is homozygous e.g. ee
- Distinguished by F2 dihybrid ratio: 9:3:4
e.g. Labrador coat colour- ee is epistatic to B gene:
yellow -E gene --> brown -B gene--> black
Cross:
P1/P2: Black (BBEE) x Yellow (bbee)
F1: all black (BbEe)
F2: 9 black (B-E), 3 brown (E-bb), 4 yellow (...ee)
29
What is dominant epistasis?
- If the first gene in the pathway is dominant the pathway is blocked
- Ratio: 12:3:1
e.g. Squash colour: W- is epistatic to G gene
white --ww--> green --G_--> yellow
F1: WwGg (white)
F2:
12 white (9xW-G- + 3x W-gg): 3 yellow (wwG-): 1 green (wwgg)
30
What is suppression?
A suppressor allele is an allele of one gene that reverses the effect of a mutation in another gene resulting in the restoration of wildtype phenotype
- Suppressor alleles may or may not have their own phenotype and can be dominant or recessive
31
What is recessive suppression?
- When a suppressor allele returns a homozygous recessive mutant of another gene to wildtype phenotype when it is homozygous recessive
e.g. purple eye colour in drosophila: recessive suppressor (s) of the recessive purple eye-colour mutant (p)
P: purple (pp;SS) x WT (PP;ss)
F1: WT (Pp;Ss)
F2: 9 WT (P-;S-): 3 WT (P_ss): 1 WT (pp;ss): 3 Purple (pp;S-)
- overall ratio: 13:3
32
What are duplicate genes?
Two genes have the same function and a dominant allele of either will produce the dominant phenotype
- Ratio: 15:1
33
Are mutations spontaneous or adaptive?
- Mutations occur spontaneously at random (not in response to the environment) but once they arise they are selected for by the environment
34
What is a somatic mutation?
A somatic mutation is a mutation that has arisen in somatic cells that is passed from cell to cell during cell division
35
What is a loss of function mutation?
- Alteration of the gene product most often leading to a loss of wildtype function e.g. product not made/has reduced activity
- Null mutation = total loss of function
- Hypomorphic mutation = partial loss of function
36
What is the difference between recessive vs dominant loss of function mutations?
- Recessive:
loss of function mutations are usually recessive because in heterozygotes 50% of the gene product is often enough
- Dominant:
Haploinsufficency: 1/2 dose of gene product is not enough to produce wildtype phenotype
Dominant-negative: the mutant protein is non-functional and interferes with the function of the normal protein in heterozygotes (often occurs in structural proteins which form dimers)
37
What is a map unit?
A map unit is the distance between two loci that will generate an increase in recombination frequency of 1%
38
How do you calculate interference?
Calculate the coefficient of coincidence:
Expected double c.o: chance of crossover between loci 1 and 2 x chance of crossover between loci 2 and 3
- Multiple that chance x number of offspring = expected number of double c.o
- C= observed number of double c.o/expected number of double c.o
- Degree of interference:
1- C
e.g. if 1-C = 0.6, then this is positive interference, 60% of double c.o's were prevented from occuring
39
What is mitotic recombination?
- A rare event that occurs in somatic cells
- Crossover and recombination is very rare during meiosis as homologous chromosomes do not pair to form bivalents
- If it does occur the two daughter cells will have a different genotype to the parent cell and will give rise to a patch of tissue called a mitotic clone
40
What is intragenic recombination?
- Recombination that occurs within a gene
41
What is RF?
Recombination frequency: Number of recombinant offspring/number of offspring total
42
What are some limitations of mapping with gene loci?
Requires:
- Alleles that give phenotypic differences
- More than one allele
43
How do you obtain a double heterozygote in:
1. Coupling phase:
2. Repulsion phase:
1. Coupling phase:
cross: pure breeding wildtype x pure breeding mutant for both genes
2. Repulsion phase:
cross: mutant for trait 1 and WT for trait 2 x WT for trait 1 and mutant for trait 2
