Week 3 Flashcards
Non-Disjunction
Anomalous chromosome numbers caused by improper segregation (aneuploidy)
Types of non-disjunction
- Non-disjunction is meiosis I: each gamete has 2 Xs or none
- Non-disjunction is meiosis II: Each gamete has 2, 1, or no Xs
Non-disjunction example in flies
ORIGINAL FINDING
- Started with white eyed female and red eyed male
- Produced all daughters with red eyes and all sons with white eyes
CYTOLOGICAL STUDIES RESULTS
- The unusual males with red eyes had one X chromosome from father and no Y (male in flies but female in humans)
- The unusual females had two X chromosomes from their mother and a Y from the father (Female in flies but male in humans)
Non-disjunction of autosomes: trisomy 21
Down Syndrome
- At least 0.3% of newborns and 25% of spontaneous abortions
- Most common form of mental retardation
- Least several viable autosomal trisomy
Non-disjunction of autosomes: Trisomy 18
Edwards syndrome X
- Severe intellectual disability, decreased muscle tone, low-set ears, internal organ defects
Non-disjunction of autosomes: Trisomy 13
Patau Syndrome
- Severe intellectual disability and other problems
- 90% die in first year of life
Chiasmata and Nondisjunction
- The rate of recombination may differ between males and females (in females more recombination in the center, in males more recombination on the tips_
- Nondisjunction is sometimes associated with chromosomes that did not recombine, which suggests that recombination may be important for proper chromosomal segregation
What are suggested mechanism for non- disjunction?
- lack of recombination
- Checkpoint failure
- age-related degradation of the cohension complex
Cohension Complex
Inhibits microtubule attachment during cell division
What 2 factors can influence sex determination?
Environmental and Genetic
Def: Genetic Sex
Based on what chromosomes an individual has; multiple types
Def: Phenotypic Sex
Based on external appearance - many species have two sexes, some have one, some have more than two
Def: Gender identity
Based on how someone feels or identifies
Sex determination in Drosophila
The X/A ratio determines gender
- Females X/A ratio of 1.0
- Males X/A ratio of 0.5
Sex determination in placental and marsupial mammals
Determined by the presence or absence of the Y-linked gen SRY
- Sexual differentiation results in a continuum of phenotypes that includes intermediates
- Genetic sex doesn’t always match the typical phenotypic sex
Development of genitals based on presence or absence of SRY gene
- Start with undifferentiated gonad, wolffian duct and Mullerian duct
SRY PRESENT - wolffian duct becomes vas deferens and gonads becomes testis
SRY ABSENT - Mullerian duct becomes fallopian tubes and gonads becomes ovaries
Congenital Adrenal hyperplasia (CAH)
- Mutations in the CYP21 gene prevent degradation of testosterone and derivatives
- In boys it results in very early pubescence
- In girls it results in an enlarged clitoris and masculinized body hair
5’-Alpha Reductase Deficiency
- Decrease in DHT production
- Leads to lack of external genitalia development until puberty
Androgen Insensitivity syndrome
Genetically male individuals have a defective androgen receptor: external appearance is female, but gonads are undifferentiated (Individuals are sterile)
ZW sex determineation
In birds, butterflies, moths, some reptiles and amphibians there is female heterogamy, meaning they are determining sex of offspring
Congenital Hypertrichosis
Excessive body hair affecting both males and females
- All carriers of the mutant allele also express the trait
Y-linked inheritance
- Exclusively male to male transmission
- Mammals have about 80 genes on the Y chromosome
- Genes on the human Y chromosome do not have homolog on the X chromosome
Dosage compensation of X-linked Genes
- In placental mammals, one X in females is silenced (X inactivation) - not 100% and different in each cell
- In fruit flies, the X in the males is upregulated (Hypertranscription)
- In nematodes, both X-linked alleles in females have lower expression (Hypotranscription)
How does X inactivation happen in placental mammals?
- Random X inactivation
- One chromosomes is coded by RNA to be transcriptionally inert forming inactive Barr body
- Descendant cells have same activation
Coat Color in cats as an application for X inactivation
- Heterozygous individuals will have one allele producing black and another producing orange
- Inactivation leads to pattern of orange and black cats
Mechanism of X inactivation in placental mammals
- Requires expression of an X-lined gene called XIST (X-inactivation-specific-transcript)
- XIST encodes a long RNA molecule that covers the chromosome to be inactivated
- XIST transcript acts in cis, meaning it only affects the chromosome from which it is transcribed
Wildtype Allele
- The most common allele
- Can be dominant or recessive
Functional effects of Mutations
WILD TYPE
- if genotype is homozygous wildtype, both alleles produce some amount of protein
NULL ALLELE
- Produces no protein
LOSS OF FUNCTION ALLELE (hypomorphic)
- produces less protein than the wildtype (diminished function compared to the wildtype)
GAIN OF MUTATIONS (hypermorphic)
- produce excess protein
NOVEL FUNCTION (Neomorphic)
- produce different protein
Dominant negative mutations
- Type of loss of function mutation
- type of mutant phenotype is often due to impaired interactions with other proteins
- interfere with the function of a wildtype allele at the same locus`
Complete Penetrance
If a genotype always produces the same phenotype
Possible causes for one genotype having multiple phenotypes
- Sex-limited traits
- Sex-influenced traits
- Incomplete penetrance
- Variable expressivity
Incomplete/partial dominance
Heterozygous individuals have a phenotype that is intermediate to each homozygous phenotype
Allelic Series
Hierarchical dominance relationships among several alleles at a locus
Co-dominance
- Heterozygous phenotype is different from either homozygous phenotype
- Not necessarily intermediate, but instead different from either homozygous phenotype
Lethal Alleles
- Inviable when homozygous
- Alters the phenotypic ratio of crosses
How do lethal alleles persist in populations?
- The onset of symptoms is during or after reproduction, passing the allele on to the next generation
- Disease causing mutation are frequently introduced into populations by de novo mutations
Mutation-selection equilibrium
- There is a balance between removal by natural selection and introduction by new mutation
Sex-limited traits
Both sexes carry genes but only one sex expresses the phenotype
- E.g. Mammalian lactation is a female-specific phenotype, horn development is males-specific in some sheep, cows and other hoofed animals
Sex-Influenced traits
Both sexes carry a gene, but the phenotype varies between the sexes
Incomplete penetrance
Traits that are nonpenetrant in some individuals but penetrant in other individuals
Variable expressivity
One genotype has multiple phenotypes that are variable
- variation is caused by interactions with other genes that may differ among individuals and/or environmental effects
Phenylketonuria
- Human disease characterized by an inability to metabolize the amino acid phenylalanine
- Over time, build up of phenylalanine causes serious problems
- Requires environmental manipulation of restricting diet
Pleiotropy
When one gene affects many phenotypes
Epistasis
The phenomenon where the effects of one gene is dependent on the alleles of one or more modifier genes
Complementary epistatic interaction
Both alleles are required for expression
- offspring phenotype proportion of 9:7
Dominant suppression epistatic interaction
The dominant expression of one allele suppresses the expression of another
- 13:3
Syntenic Genes
Genes on the same chromosome
Linked genes
Syntenic genes that are so close together that their alleles cannot be sorted independently
Purpose of genetic linkage mapping
Plots the positions of genes and their relative distances from each other on chromosomes
