Ch. 3 Extension of Mendelian Genetics Flashcards
Was Mendel Wrong?
After the rediscovery of Mendel’s Laws of inheritance in the early 1900s, scientists and agriculturists tried to repeat Mendel’s experiments.
Many confirmed Mendel’s finding, but many others did not
Campions petal color and foliage cross showed what?
Did not show a 9:3:3:1 distribution in the F2 generation as Mendel has expected
What test is used to compare the observed and expected values?
Chi-square test.
Is deviation due to change or not?
Chi- square formula
x^2= the sum of (observed - expected)^2/expected
Degrees of freedom
n-1 (group size-1)
How do you compare chi square to critical value?
If chi-square is smaller than the critical value, fail to reject the hypothesis. Means that deviation was due to chance.
If chi-square is larger than the critical value, reject the hypothesis. Deviation is not due to chance.
Basic principles of gene transmission (Mendel’s Laws)
Genes are present on homologous chromosomes.
Chromosomes segregate and assort independently during meiosis and the formation of gametes.
Alleles are transmitted from parent to offspring following Mendelian rules.
Alleles can change phenotypes (what Mendel didn’t know)
Alleles often do not display a dominant/recessive relationship.
Phenotypic ratios are not always 3:1 or 9:3:3:1 as expected following Mendel
What are alleles?
Different versions of a gene.
Impact how a gene is expressed.
If the gene is expressed (translated) into a protein, an alternative allele might be expressed into a different gene product (a different protein).
Different proteins (or the lack of) impact the phenotype differently.
What is the relationship between genes and protiens?
Gene -> protein -> phenotype
Garden pea plant Sbe1 gene (starch branching enzyme)
sbe1 enzyme- catalyzes the formation of highly branched starch molecules during seed maturation.
sbe1 gene has 2 alleles:
R- codes for functional Sbe1 protein
r- codes for non functional sbe1 protein
Garden pea
R and r alleles - nucleotides
R - represents 3500 nucleotides
r - represents 3500 nucleotides plus an additional 800 nucleotides that make the gene non functional
Garden pea
Wrinkled gene
Wild type (R) encodes for Sbe1 - catalyzes the formation of highly branched starch
Mutant (r) is not coding for this enzyme, hence wrinkled seeds lack enzyme activity.
No enzyme activity -> more sucrose -> water moves in by osmosis, causing the pea to expand inside its seed coat. Once seed matures it loses the water as it dries and shrivels. But having been stretched, the seed coat then wrinkles as the pea inside shrinks -> wrinkled appearance.
Wild type allele
The allele which normally occurs in a wild population, most frequently, often (but not always) dominant. Responsible for the wild type phenotype.
Mutant allele
Alternative alleles resulting in altered gene product.
Arises through mutations.
Responsible for the mutant phenotype.
What are the types of mutant alleles?
Loss of function mutation
Gain of function mutation
Neutral mutations
Loss of function mutation
(hypomorphic, amorphic) gene is coding for an enzyme, mutation causes reduction or elimination of that enzyme (null allele) wrinkled gene is an example
Metabolic disorders
Gain of function mutation
(hypermorphic) mutation enhances function of wild type, excess gene product (ex: conversion of proto-oncogenes which regulate cell cycle to oncogenes where regulation is overridden by excess gene product -> cancerous cell)
Neutral mutation
No change to the phenotype, no change to the evolutionary fitness of the organism (use in phylogenetics and population genetics- can see mutations in sequence of DNA)
Genes function to produce polypeptides
Most genes are translated into polypeptide (amino acid chains); alteration of genes causes alteration in the polypeptide chains.
(Mutations in a gene cause alterations in polypeptide chain and that can influence the expression in the phenotype)
Wild type allele produces what type of polypepetide?
A functional polypeptide.
Wild-type phenotype
Recessive amorphic loss of function allele produces?
Does not produce a functional polypeptide.
Server mutant phenotype.
Recessive allele
Recessive hypomorphic loss of function allele produces?
A partially functional polypeptide.
Mild mutant phenotype.
Recessive allele
Dominant negative allele produces?
A polypeptide that interferes with the wild-type polypeptide.
Severe mutant phenotype.
Dominant allele
Amorphic
protein is completely different and non functional
Hypomorphic
protein is slightly different, still functional, but less active
Wild type and amorphic genotype produces?
Wild type phenotype
Mutant allele is recessive
Wild type and hypomorphic genotype produces?
Wild type phenotype
Mutant allele is recessive
Wild type and dominant genotype produces?
Mutant phenotype
Mutant allele is dominant (mutant gene blocks the wild type one)
Dominant allele symbols
indicated by italic uppercase letter (D) or letters (Wr)
Recessive allele symbols
indicated by either an italic lowercase letter (d) or italic letter or group of letters (wr)
Mutant alleles symbol
indicated by italic letter (e)
Wild type allele symbol
indicated by italic letter plus superscript + (e^+)
Nutritional mutants in bacteria
Which amino acid they can or can’t synthesize
leu- refers to mutant which cannot synthesize amino acid leucine, the wild type bacteria would be leu+
Mutants in humans
capital, italicized letters are used to name genes: BRAC1, one of the genes associated with susceptibility to breast and other cancers
What are the types of dominance?
Complete dominance
Incomplete dominance
Codominance
Dominance does not alter the way the genes are inherited, it only influences what?
Influences the way the genes are expressed as a phenotype
Incomplete or partial dominance
The phenotype of the heterozygote is midway between the phenotypes of the 2 homozygotes.
One allele is partially, or incompletely, dominant over the other.
Is incomplete dominance the same as the blending hypothesis?
NO. When you cross 2 heterozygous (pink) plants, the homozygous phenotypes (red and white) reappear. If the blending hypothesis was true, pink parents would cause offspring to be even lighter and the alleles would get watered down through generations.
Tay-Sachs Disease - what is it?
Rare recessive autosomal disease.
2 unaffected heterozygous parents (Aa) have a probability of 1/4 of having a child with TSD (aa).
Infants unaffected at birth until 6 months, progressive loss of mental and physical state, leads to death usually by 2-3 yrs.
Tay-Sachs Disease - Incomplete dominance
Responsible gene, encodes for alpha subunit of the Hex-A enzyme (hexosaminidase).
Hex-A in lysosomes breaks down a lipid component (ganglioside, GM2) of nerve cell membranes.
Without functional Hex-A, GM2 accumulates within neurons in bran (loss of function mutation).
TSD results from loss of activity of enzyme Hex-A.
Heterozygous carriers (Aa) produce 50% of normal amount of Hex-A - intermediate level of enzyme
Carriers (Aa) show no symptoms of the disorder
Codominance
Neither allele is dominant over the other.
Heterozygous expresses the phenotypes of both homozygotes.
Ex: Coat color in longhorn - appears blended but actually red and white independent hairs
Complete dominance
phenotype of the heterozygote is the same as the phenotype of one of the homozygotes
What if there are more than 2 alleles?
An individual can only have 2 alleles at a distinct gene locus (bc only 2 chromosomes), but multiple alleles can exist within a population at a distinct gene locus.
EX: blood types
Multiple alleles # of genotypes formula
Number of genotypes = [n(n+1)/2]
n= number of alleles
If there are more than 2 alleles which one is dominant/recessive/codominant/incomplete?
You have to breed the rabbits to get heterozygotes and see what the fur color is
Allelic series
Sort alleles by dominance. c+ dominant over cch, ch, c Cch partially dominant over ch and c (partial bc new phenotypes appear) ch dominant over c c recessive to everyone c+>cch>ch>c
ABO blood groups
IA-encodes A antigen
IB-encodes B antigen
i-encodes no antigen (O)
6 genotypes: 3 diff heterozygous and 3 diff homozygous
ABO blood groups - dominance order
IA>i IB>i IA=IB (codominant) 4 phenotypes - A,B,O,AB i is recessive
What is the universal donor?
O
What is the universal recipienct?
AB
Visible mutations
mutations which change morphology (seed color, eye color, fur color, enzyme concentration) most of them are recessive.
(don’t necessarily see it, you can measure it to identify it)
Sterile mutations
mutations that prevent reproduction
Lethal mutations
mutation which interfere with vital functions - deadly
Essential genes
absolutely required for survival
Mutations in essential genes can be tolerated if?
They are heterozygous.
One wild-type allele is sufficient for survival
What happens to a homozygous recessive person with lethal alleles?
Homozygous recessive will not survive.
Mutation behaves as recessive lethal allele.
Time of death depends on when the essential gene product is needed.
Recessive lethal allele in mice
There are no A^Y A^Y homozygous yellow mice because they die before born (embryonic lethal).
Since it is lethal, you would say probability of being A+ A+ (wildtype) is 1 out of 3 instead of 1 out of 4.
Huntington’s disease is what kind of allele?
A dominant lethal allele
Hintington’s disease
Dominant autosomal allele H
Causes progressive degeneration of nervous system, dementia, and early death.
Onset of disease is around 40
In general, dominant lethal alleles are very rare.
If all affected individuals die before reaching reproductive age, mutant gene will not be passed onto next generation and disappears from the pop.
To persist in a pop, affected individuals must have offspring before the lethal allele is expressed.
T/F 2 modes of inheritance can happen at the same time
TRUE
If we are considering 2 genes which do not follow Mendelian inheritance, then what still applies?
Mendel’s law of independent assortment still applies
What happens to the ratio when 2 modes of inheritance are expressed at the same time?
The phenotypic ratio among the offspring will deviate from 9:3:3:1
Results in many variants of modified ratios
Pleiotropy
one gene affects many phenotypic characters
EX: Phenylketonuria - recessive allele, if untreated causes intellectual disabilities, blue eyes, and light skin)
Pleiotropy
Marfan syndrome
Genetic disorder of CT; autosomal dominant mutation in gene that encodes glycoprotein fibrillin, results in multiple phenotypic effects: tall, thin, long arms legs fingers toes; flexible joints and scoliosis
Phenotypic characters (hair color, eye color, fruit shape) can be influenced by what?
Many different genes and their gene products.
This does not necessarily mean 2 or more genes directly interact with each other.
Cellular function of numerous gene products contributes to development of what?
common phenotype.
Ex: over 50 genes are involved in ear development, mutations that interrupt the developmental steps can lead to the common phenotype hereditary deafness in humans
Polygenic Inheritance
A single character can be determined by multiple genes
Common in continuous (quantitative characters) - height and skin color
Skin color- determined by 3 genes, gives continuum of colors
Direct gene interaction
Genes at 2 loci interact to produce a single characteristic
EX: fruit color in peppers
2 genes at 2 different loci, both with a dominant and recessive allele
Epistasis
Expression of 1 gene masks (hides) the effect of another gene at a different locus (similar to dominance, except that in dominance one allele masks the other at the same locus)
Epistasis
Lab coat colors
Depends on 2 genes
One gene determines the pigment color (B black, b brown)
The other gene determines deposition of the pigment in the hair shaft (E color, e no color)
BLONDE labs- have alleles for black and brown color, but because they are homozygous recessive for e (ee) the pigment is not deposited in hair
Gene products can interact with each other?
YES. often hormones
Sex linked inheritance
genes located on sex chromosomes
Sex influenced inheritance
sex determines how allele is expressed
Sex influenced inheritance
Male pattern baldness
Allele B behaves dominant in males and recessive in females
If BB genotype in females, phenotype is less pronounced.
Bb in female not bald, Bb in male is bald - dominant allele expressed in male but not female
Sex limited inheritance
Expression of an allele is limited to a particular sex
Sex limited inheritance
Feather plumage in chickens
Caused by an autosomal gene
Hen feathering controlled by dominant allele (H) expressed in both sexes
Cock feathering controlled by recessive allele (h) only expressed in males
hh in females - hen feathered
hh in males - cock feathered
Phenotypic expression of a trait can be influenced by what 2 things?
By genotype and by environment
Environment on phenotypic expression
we assume that dd dwarf plants will always be dwarf, like they grow in a closed system where the presence or absence of a gene product directly determines the whole phenotype. That is not the case.
Organisms exist in diverse environmental conditions- can influence how genes are expressed (water, fertilizer can influence height of plant)
Penetrance
percentage of expression of the mutant genotype in a pop
how common the mutant is in in the pop
Expressivity
The degree or range of expression of the mutant phenotype
The mere presence of a gene does not guarantee its expression.
Results from the influence of other genes and environmental factors.
Incomplete Penetrance
A recessive disease is 70% penetrant - means an individual w genotype aa is 70% likely to develop the disease
70% of the aa people will show symptoms, and 30% do not show symptoms because of incomplete penetrance
BRCA 1 and BRCA2 are genes associated with inherited forms of cancer.
Mutant alleles cause a higher chance of developing tumors, but not all affected individuals will
Reduced penetrance probably results from what?
A combination of genetic, environmental, age and lifestyle factors, many of which are unknown.
Susceptibility for colon cancer - can see if you have mutant allele, can change lifestyle to reduce risk
Incomplete Penetrance
Polydactyly
Dominant mutation P.
Some individuals do not express the trait even though they are PP or Pp.
Dominant so every affected person has at least 1 affected parent.
Person - inherited dominant allele but does not express it even though they are Pp, passed it on to offspring.
(Variable) Expressivity
Often traits are not expressed uniformly among all individuals that show them.
Polydactyly - some people have extra fingers and toes which are fully functional, whereas others possess only a small tag of extra skin
Variable Expressivity
Lobe Eye Mutation
all flies pictured are heterozygous for dominant mutation, but phenotypes vary from small eye to nearly wild type eye.
Human Eye colors (penetrant and expressivity)
Brown eyes
Production of proteins melanin determines eye color.
Brown eye is fully penetrant because we all have some amount of brown in our eyes, but the expressivity of brown eyes is variable.
Human eye colors
Range of colors
Eyes with very little melanin in the iris are blue (there is no blue pigment) eyes with a bit more melanin are green, hazel or light brown, and those with high concentration of melanin are medium or dark brown
Does eye color follow Mendelian rules?
YES.
B (brown) and b (blue) are dominant and recessive, and the inheritance follows Mendelian rules, but with variable expressivity.
Complete penetrance vs. Incomplete penetrance
Identical known genotypes yield 100% expected phenotype.
Identical known genotypes yield less than 100% expected phenotype.
Consistent Expressivity vs. Variable Expressivity
Identical known genotypes with no expressivity affect yield 100% expected phenotype.
Identical known genotypes with an expressivity effect yield a range of phenotypes.
Incomplete penetrance with variable expressivity
Identical known genotypes produce a broad range of phenotypes, due to varying degrees of gene activation and expression
Genes act in what context?
In the context of the genotype/in the context of other genes
In the context of the environment
Incomplete penetrance and variable expressivity are due to what effects?
The effects of other genes and environmental factors.
Conditional Expression of Genes
Rearing temperature effects
Siamese cats and Himalayan rabbits
Darker fur on cooler areas of body (tail, feet, ears)
Temperature sensitive allele responsible for pigment production
Nutritional mutations
Prevent synthesis of nutrient molecules in bacteria
Auxotrophs (microbe)
Phenotype expressed or not depending upon diet
Examples of nutritional mutations in humans
Phenylketonuria - loss of enzyme to metabolize amino acid phenylalanine. Have severe probs unless low-Phe diet
Lactose intolerance - cannot metabolize lactose
Cytoplasmic Inheritance
In Eukaryotes, DNA and genes are not only found in the cell nucleus, but some characteristics are encoded by genes located in the cytoplasm in cell organelles.
Mitochondria and chloroplasts, both containing DNA, are usually inherited from a single parent (typically maternally, but not always)
Cytoplasmic genes in the cell organelles are usually passed how?
With the egg cell from mother to offspring.
The trait is always passed from mother to daughters and sons, but never from father.
Cytoplasmic inheritance
Variegation in 4 o’clocks
The phenotype of the offspring are determined by the maternal parent, never by the paternal parent.
The trait is caused by loss of function mutation in the DNA in the chloroplast.
Cytoplasmic Inheritance
Rare disorders
Some (rare) disorders in human exhibit cytoplasmic inheritance and arise from mutations in the mitochondrial DNA.
Mostly genes encoding the electron transport chain.
LHON (Leber hereditary optic neuropathy) - loss of vision during early adulthood caused by dying nerve cells of the optic nerve.
The phenotype of an offspring is determined by the genotype of the mother, although the genotype is inherited from?
Both parents
Cytoplasmic inheritance
Shell Coiling
Arise when substances present in the cytoplasm of an egg (encoding by the mother’s nuclear genes) are pivotal during early development
Nature vs. Nurture Debate
How much of what makes a person is genetically determined and how much is environmentally determined?
Genetic determinism (Eugenics Movement) - like father like son.
Blank slate hypotheses.
Today still a hot topic in the fields of Behavioral Sciences and Psychology.
Today: both genetic and environment contribute to a phenotype, but at different ratios
Bipolar disorder: 69% genetics, 32% environment
Eating disorder: 40% genetics 60% environment
Epigenetics: The link between nature and nurture
- What is the definition of incomplete dominance?
The heterozygote has an intermediate phenotype
- What is the definition of wild type allele?
the original, most prevalent allele in the population
- Horses can have a white coat (CW) or red coat (CR). When horses that are homozygous for each of these alleles are crossed, the offspring all have a roan coat, meaning some of their hairs are white , and some are red. This is an example of?
Codominance
- Maple syrup urine disease is a genetic disorder in humans characterized by the inability to break down chain amino acids. Humans who are identified and who eat a diet low in these amino acids grow up to function normally. Individuals who are not diagnosed and do no eat the special diet have wide ranging effects including developmental delays and early death. Maple syrup urine disease is:
Influenced by environmental factors
- Alzheimer’s patients who inherit the mutant allele can exhibit a range of phenotypes, ranging from mild cognitive impairment to severe dementia. This is an example of:
Variable expressivity
- A cross between a Mexican hairless dog and a hairy dog yields 50% hairless and 50% hairy offspring. However, a cross between 2 Mexican hairless dogs yields 30& hairless and 70% hairy dogs. How do you explain the results?
The hairless allele (H) is dominant to hairy, but its homozygous is lethal.
- The BRAC1 and BRAC2 mutations are responsible for increased risk for breast and ovarian cancer. Men with the mutations do not develop breast cancer as often as women with the mutation. This is an example of:
sex-influenced expression AND incomplete penetrance
- Individuals with albinism often have a variety of symptoms including changes in skin pigmentation, as well as visual problems. This is an example of:
pleiotropy
- In a mating between individuals with the genotype IAIB x ii, what percentage of the offspring are expected to have the O blood type?
0
- With _____ there will be more than 2 genetic alternatives for a given locus.
multiple alleles
