Genes Flashcards
what is a gene?
a part of a chromosome involved in the transcription of DNA to RNA
what are the 4 stages in the cell cycle?
G1 - first growth phase
S - DNA synthesis and replication phase
G2 - second growth phase
cytokinesis - actual division of the cell
what is the function of independent assortment?
to generate different combinations of chromosomes in genes
what is the function of crossing over?
to generate different combinations of alles in chromosomes
what are some features of a monohybrid cross?
- includes one gene locus with two alleles
- 3:1 phenotypic ratio in F2 generation
what are some features of a dihybrid cross?
- invovles two genes
- 9:3:3:1 phenotypic ratio in the F2 generation
what are different forms of genes known as?
alleles
true or fale: gain of function mutations are dominant, and loss of function mutations are recessive
true
what is incomplete dominance?
when a heterozygous phenotype is intermediate between the two homozygote phenotypes
what is codominance?
when heterozygotes show phenotype of both alleles
- e.g. blood group AB has both type A and type B characteristics
what is pleiotropy?
when one gene may influence more than one trait
what are lethal alleles?
alleles that cause an organism to die only when present in a homozygous condition
- e.g. yellow allele in mice being dominant for coat colour, but recessive for lethality
- Ay = yellow gene - if mouse has genotype Ay A, it will be born with yellow coat
- if mouse has genotype Ay Ay, it will not survive
what is phenotypic variability?
the phenomena when individuals with the same genotype show different phenotypes
what is penetrance?
the measure of the % of individuals with a given genotype who expressed the expected phenotype
- e.g. take a group of 5 individuals with the same genotype, but only 3 of them express the expected phenotype; phenotype is therefore 60% penetrant
what is expressivity?
the measure of the extent to which a given genotype is expressed at the phenotypic level
e.g. take a group of 5 individuals with the same genotype, and all 5 express the phenotype. penetrance is 100%. however, all individuals express the phenotype only to a certain extent. e.g. one individual will have very very light blonde hair, whereas the other 4 will have varying shades of blonde hair.
what is epistasis?
the interaction between two or more genes to control a single phenotype
e.g. the allele of one gene can mask the phenotypic effect of an allele of another gene
what phenotypic ratio arises in the case of recessive epistasis?
9:4:3
what phenotypic ratio arises in the case of dominant epistasis?
12:3:1
what is epigenetics?
“heritable changes in gene expression that do not involve alterations of the DNA sequence”
how can epigenetics regulate gene expression?
- environmental factors can switch on expression of genes (e.g. red and green gene)
- some genes that are expressed are transient, and this gene is not expressed in daughter cells
- some gene expressions persist throughout generations, meaning an epigenetic effect has occured
How can DNA methylation or histone modification in general affect gene expression?
- DNA methyl. and histone mods. can alter chromatin structure
- chromatin structure affects gene expression
- this means that the altered chromatin structure can be passed on to daughter cells
what is paternal imprinting?
- when the paternal allele is imprinted and silenced by epigenetic tags
- this means that the maternal allele is preferentially expressed in the embryo
what is maternal imprinting?
- when the maternal allele is imprinted and silenced by epigenetic tags
- this means that the paternal allele is preferentially expressed in the embryo
what is the function of genomic imprinting?
- the genetic conflict hypothesis - conflict between interest of maternal + paternal genes in the foetus
- father may only be related to a subset of foetuses (as female may mate with others) and wishes to increase the survival chances of his offspring by promoting their growth
- mother equally related to all offspring and wishes to divide resources equally between all of them
what is an autosome?
any chromosome that isn’t a sex chromosome
how can it be that an individual with XX chromosomes is a male?
- only one gene on the Y chromosome is required - the SRY (sex-determining region on Y)
- translocation of SRY to the X chromosome causes the individual the be male
- the same thing can occur if the SRY is mutated on the Y chromosome, leading to XY females
how does the SRY gene confer maleness?
SRY = DNA binding protein (transcription factor)
- regulates expression of genes necessary for testis formation
- SRY expression changes the indifferent gonad to the testis
what is a gyandromorph?
- a sexual mosaic (normally just in birds)
- cells on the right side of the body express ZW (female chromosome set)
- cells on the left side of the body express ZZ (male chromosome set)
what is sex-linked inheritance?
- usually involves genes located on the X chromosome (X-linkage)
what is a barr body?
- dosage compensation for female X-chromosomes
- female mammals have double the gene dosage of X-linked genes
- one X chromosome in each female cell becomes inactivated
- this inactivated X chromosome is a barr body
what is the purpose of gene maps?
- identifying genes responsible for diseases or traits
- compare genome organisation between organisms
What does it mean to say that females are the homogametic sex and males are the heterogametic sex?
Females have XX, males have XY
What is the function of Giemsa in human cytogenetic mapping?
Cause G-banding on human chromosomes to make dark (G-dark) and light (G-light) bands
What is Genetic Linkage?
Genes on the same chromosome may violate Mendel’s second law of independent assortment as they are linked
- alleles of genes on the same chromosome will segregate together in gametes during meiosis UNLESS crossing over occurs to separate them (crossing over occurs at random positions along chromosome)
How do you calculate frequency of recombinant genes & how does it relate to distance?
No. Of recombinant gametes / total number of gametes (e.g. 4 recombinant gametes / 16 total gametes = 25% recombinant)
The frequency of recombinant gametes is proportional to the frequency of crossing-over ( and therefore distance apart on the same chromosome)
What do recombination frequencies tell us? (<50% and >50%)
- > 50% = genes on different chromosomes (ind. assortment) or genes far apart on same chromosome
- <50% = genes linked on same chromosome - smaller the RF, closer the genes
How is genetic distance (recombination frequency) calculated?
RF = ( no.of recombinant progeny x 100 ) / total number of progeny
Unit = centimorgans
When doing a pedigree diagram, what does generation skipping mean?
The allele is recessive
What is genetic heterogeneity?
Having mutations in different genes that give the same disease
- e.g. at least 3 genes causing familial early-onset Alzheimer’s disease
What makes doing a pedigree diagram difficult?
- incomplete penetrance
- genetic heterogeneity
- non-paternity / misattributed paternity
What are some commonly used DNA markers?
- Short tandem repeats (STRs)
- Single nucleotide polymorphisms (SNPs)
What are short tandem repeats? (STRs)
- microsatellite repeats
- tandem repeats of a short sequence
- usually noncoding sequences
What are single nucleotide polymorphisms? (SNPs)
- single nucleotide differences between individuals
- e.g. one nucleotide difference will be found between individuals in every 1000 nucleotides
What is the principle of linkage analysis with SNPs?
- disease causes mutation
- mutation occurs in base closest to SNP1, and further downstream are SNPs 2 and 3
- crossing over occurs between the mutant base and SNPs (linkage)
- SNP2 shows linkage in some pedigrees as it is relatively far away from mutation, whereas SNP1 shows linkage in all pedigrees as it is closest to mutation
- SNPs used as markers to determine position of mutation
What is positional cloning of the disease gene?
selecting ‘candidate genes’ in the region of the chromosome and looking for disease-associated mutations in each candidate gene
-genetic cluedo
How does next generation sequencing (NGS) aid with disease gene discovery?
- sequence whole genomes or whole exomes from unaffected and affected members of a pedigree
- identify rare variants shared by affected members
- identify causative variants in candidate genes + investigate the functional consequences of the causative variants
What is aneuploidy?
A chromosome abnormality where the number of chromosomes is abnormal
What is the normal human karyotype? (Complete set of chromosomes)
46 chromosomes, XY = males, XX = females
What is monosomy?
Loss of a single chromosome
What is trisomy?
Gain of one extra chromosome
What is tetrasomy?
Gain of an extra pair of chromosomes
How can aneuploidy arise?
Mistakes in chromosome segregation (non-disjunction) during meiosis can give aneuploid gametes
How is prenatal screening for Down syndrome performed?
- pregnant women offered ‘combined test’ to identify pregancies with higher risk of aneuploidy (only shows RISK)
- chorionic villus sampling (CVS) used to sample foetal cells
- karyotype of foetal cells determined
What is genetic mosaicism?
Where individuals have a mixture of normal and trisomy cells
- can be another cause for Down syndrome
What is Turner syndrome a result of?
monosomy
What are some syndromes caused by Trisomy?
- Klinefelter syndrome
- triplo-X
- XYY syndrome
What is the correlation between maternal age and incidence of trisomy?
As age increases, so does risk of trisomy in women - leads to increased frequency of miscarriage
At what phase does 95% of maternal non-disjunction occur to induce trisomy?
- prophase 1
- caused by a premature loss of cohesion in prophase 1, which gives 2 univalents that segregate independently - gives aneuploid gametes
What types of genes are found in mitochondrial genomes?
- mtDNA
- contains structural genes for proteins involved w/ oxidative phosphorylation
What types of genes are found in the chloroplast genome?
- cpDNA
- contains structural genes for proteins involved in photosynthesis
How does maternal inheritance of mtDNA work?
- in mammals, paternal mitochondria + other sperm components destroyed after fertilisation
- females transmit traits of extranuclear genes to all offspring
- males never transmit traits of extranuclear genes
What are some differences between Mendelian and complex traits?
Mendelian
- single gene w/ high penetrance
- predictable mode of inheritance
- simple relationship between genotype and phenotype
Complex
- multiple genes w/ low individual penetrance
- familial clustering - inheritance not predictable
- complex relationship between genotype + phenotype
- often affected strongly by environment
What is an example of genetic and environmental influences on a complex trait?
Type 2 diabetes
Genetic - if both parents affected, risk increased by 75%
Environmental - if BMI is >30% (obesity), risk increases
True or false: complex genes can be continuous or discontinuous?
True
How is total phenotypic variance calculated?
Vp = Vg + Ve
Vp = total phenotypic variance
Vg = genetic variance
Ve = environmental variance
What does it mean to have a high heritability?
- Genetic differences in a population explain a high proportion of the phenotypic variation
- i.e. genes affect the phenotype more
Low heritability = more easily affected by the environment
What is concordance in relation to twins?
Concordance = probability that if one twin is affected by a trait, the other twin is also affected
- concordance = 1 (one twin is affected, other twin is always affected)
- concordance = 0.6 (one twin is affected, other twin has 60% chance of being affected)
Difference in concordance between MZ and DZ twins can be used to estimate heritability
Why are disease-associated alleles common?
- late-onset diseases have little effect on fitness (weak purifying selection)
- alleles that were advantageous or neutral in the past may confer disease susceptibility in modern society
- disease causing alleles can be maintained at high frequency by balancing selection
What is Genome wide association studies (GWAS)?
- a population-level approach to disease gene mapping
- help to identify disease associated SNPs
What is a haplotype ?
- closely linked SNPs on the same chromosome that are usually inherited together in ‘haplotype blocks’
- gaps between haplotype blocks are areas where crossing over occurs preferentially
- crossing over never occurs within haplotype blocks
What is linkage disequilibrium?
The co-inheritance of SNPs in a haplotype block
What does linkage equilibrium mean for haplotype frequency?
- each haplotype is present at frequency expected from allele
- e.g. with genes A, a, B, and b, there are equal frequencies of AB, aB, Ab, and ab
