Human Genetics Flashcards
What is an allele?
The type of a particular characteristic that is determined by a gene.
What does heterozygous mean?
Individuals with two different alleles.
What does homozygous mean?
Individuals with two copies of the same allele.
What is a genotype?
The genetic constitution, summing all of the alleles.
What is a phenotype?
The observed form of a characteristic in an organism.
What is the exome?
The DNA sequence that is complementary to all the mRNA produced from the genome.
What is the principle of segregation?
- Characteristics are determined by genes, existing in pairs in each organism.
- Each gamete contains only one of each pair- which is entirely random- and therefore these factors segregate.
- The Union of male and female gametes is a random process that reunites pairs of genes.
What are the two observations that make up the basis of genetics?
- One form of life always gives rise to other individuals of the same type.
- While there is individual variation within a species, that variation is not random since individuals have a tendency to resemble their ancestors.
What is a null mutation?
A mutation that results in the loss of gene function.
What is a hypomorph mutation?
A mutation that results in partial gene function.
Examples of gain of function mutations
Dominant active, dominant negative, Neomorph, hypermorph and antimorph
What is a Neomorph mutation?
A gain of function mutation that results in the introduction of a new function.
What is a hypermorph mutation?
A gain of function mutation that results in more of the original gene function.
What is an antimorph mutation?
A gain of function mutation where the function gained inhibits the wild type gene function.
What is a silent mutation?
A mutation that does not affect gene function.
What is an example of a dominant active mutation?
Mutation of the Ras gene, which causes a GTPase to become constitutive.
Three gene sites sensitive to null mutations
- Mutation in the conserved region of a promoter sequence, inhibiting transcription.
- Mutation in an enzyme’s active site, changing the structure/function of the enzyme.
- Mutation in an intron, meaning that the intron is not removed during splicing, and incorrect proteins are produced.
Example of a gene site sensitive to a hypomorph mutation
Mutation at the edge of an enzyme’s active site, resulting in a slight change to the enzyme structure.
Example of a gene site sensitive to silent mutations
Mutation anywhere other than the active site of an enzyme.
Define Haplosufficient
A gene which has enough function in a heterozygote to be functionally wild type.
Define haploinsufficient
A gene which does NOT HAVE ENOUGH function in a heterozygote to be functionally wild type.
- one copy of the wild type allele is not enough
- cannot function if one allele is mutant
Which types of mutant alleles are normally recessive?
Alleles that have resulted from either null mutations or hypomorph mutations.
Which types of mutant alleles are normally dominant?
Alleles that resulted from gain of function mutations.
- dominant active, dominant negative, Neomorph, hypermorph, antimorph
Define dominant allele
The trait that is shown in the heterozygote.
Define recessive
The trait that is hidden in a heterozygote and is only visible in a double recessive homozygote.
How did Mendel’s peas show complete dominance?
In all of the crosses that Mendel did, the heterozygote had the same phenotype as the homozygous dominant.
An example of a gene that is not completely dominant/recessive
The MCR1 alleles for red hair are not completely recessive as some heterozygotes have red hair.
A snapdragon can appear pink as a result of a cross between a red plant and a white plant as the alleles are codominant, as the red allele isn’t completely dominant and the white allele isn’t completely recessive.
What is pedigree analysis?
Inference of the random human mating that must of occurred in previous generations, used to follow genetic inheritance.
What are the features of dominant inheritance?
Dominant traits are present in all generations.
Two individuals with a dominant trait can still produce homozygous unaffected progeny.
What are the features of recessive inheritance?
Recessive traits can skip a generation- can get affected individuals from unaffected parents.
Shows individuals who must have been carriers of the recessive allele in pedigree diagrams.
Recessive traits can only be seen if both alleles are mutant and not wild type.
If there is mating between two affected parents, all progeny are affected.
What is a wild type allele?
The most frequent allele of a gene.
What is a mutant allele?
All alleles other than the wild type allele for a particular gene.
Define polymorphic and give an example of a polymorphic gene.
Several alleles of a gene are all frequent, even if one is more rare than another, and no allele is chosen as wild type, e.g. blood group gene.
What is a heteromorphic pair? What is an example of a heteromorphic pair?
A pair of chromosomes that are not homologous and do not look alike, are in different forms.
An example are the X/Y chromosomes in humans.
What are heteromorphic pairs associated with and where are they found?
The heteromorphic pair are the sex chromosomes. In one sex, there is the heteromorphic pair and in the other sex there are two copies of one member of the heteromorphic pair.
What are autosomes?
Chromosomes which are identical in both sexes, e.g. Chromosomes 1-22 in humans.
How do the X and Y chromosomes behave in meiosis?
As homologues.
The Y chromosome from a father must go to a son and the X to a daughter.
The X chromosome in any male must have come from their mother.
Half the population in any generation have a Y chromosome.
Define Nondisjunction.
Exceptionary behaviour of chromosomes, e.g. In Down’s syndrome
What is a lethal allele?
Alleles that cause death when present in a homozygote.
What is phenylketonuria?
It is a disease caused by a rare recessive allele. The allele means that the phenylalanine hydroxylase enzyme cannot convert Phe to Tyr.
How is phenylketonuria diagnosed and treated?
It is diagnosed at birth using a Guthrie test which uses a PKU antibody to check for the enzyme in a baby.
It is treated by a low protein diet, which limits Phe build up in the cerebrospinal fluid.
What is independent assortment?
Alleles of a particular gene are inherited independently to the alleles of another gene
Explain the 9:3:3:1 ratio
Mendel looked at two genes, when crossed it produced a doubly heterozygous F1 generation. Allowing this F1 to self-fertilise produces progeny that are either dominant for both characteristics, dominant for one or the other or recessive for both, in the ratio 9:3:3:1.
What is the trihybrid ratio?
27:9:9:9:3:3:3:1
What are the properties of the chi squared test?
- appropriate if p doesn’t equal q
- appropriate if there are more than two outcomes
- not appropriate if the number of expected is small
What is epistasis?
The interaction of different genes, which causes one gene to mask the phenotype of another gene.
What is linkage?
When genes are on the same chromosome, there is a tendency for alleles of those genes to be inherited together.
What are recombinants?
New combinations of non-parental alleles produced from the inheritance of linked genes. Result from crossing over.
What are the parental types/non-recombinants?
The parental combinations of alleles.
How can gene order be determined?
The frequency of recombinants indicates the strength of linkage and the distance between genes. If genes are closer together they are more likely to be inherited together.
What is a centimorgan?
The unit of 1% recombination frequency (1cM).
What is crossing over?
The breaking and rejoining of homologous chromosomes at homologous positions.
What happens if crossing over occurs in an egg or a sperm cell?
New recombinants are seen in the progeny.
What was Stern’s experiment and what did it prove?
Looked at Bar(B) and Car(C) recombination on the X chromosome of Drosophila where the mother had 2 abnormal X chromosome.
The first one was missing the terminal part of the X.
The second one had a visible second arm from the Y chromosome.
The F2 progeny had both:
- parental combinations of genetic traits and chromosomal abnormalities.
- recombinants for both genetic traits and chromosomal abnormalities.
This proved that physical exchange accompanied genetic exchange.
Give three reasons for mapping genes.
- To design and make complex genotypes for experimental or commercial purposes.
- To identify an unknown gene relative to other known genes.
- To make comparisons between evolutionarily related species.
What is genetic mapping by pairwise comparison?
For two genes on the same chromosome, do a test cross to find the homozygous recessive parent. The test cross is between a dihybrid and the double recessive homozygote. All the genes transmitted by the rest of the progeny are shown as a phenotype.m
Why are all the genes transmitted by the progeny in a dihybrid test cross shown as a phenotype?
Dominant alleles are shown instead of the parent recessive allele. Recessive alleles also show as a phenotype in the progeny as the parent is recessive so get recessive homozygotes in the progeny.
Why would a trihybrid test cross be used?
It is quicker to look at more genes at one time.
In a trihybrid test cross, why must the triply dominant heterozygote be crossed to the triply recessive homozygote?
Otherwise the dominant allele could mask genotypes.
What are the limitations of genetic mapping?
- need data for a large number of progeny
- need genes that are close together, otherwise the frequency of recombination would be underestimated
What is interference?
There are fewer numbers of double crossovers than expected, meaning that when one exchange event occurs it interferes with the next event occurring locally.
What is the coefficient of coincidence?
The observed number of double crossovers divided by the expected number of double crossovers.
What does C = 1 mean?
Independence in the inheritance of linked genes.
What does C = 0 mean?
There is complete interference in the inheritance of the linked genes.
When no double crossovers occur in a region, there is only ever one exchange in that region.
These exchange events physically interfere with each other as the genes are too close together.
What is the expected number of double crossovers?
P (crossovers in regions 1+2) = P (crossovers in region 1) x P (crossovers in region 2)
Using recombination, what is found when linkage is measured between different genes?
- Some genes are linked, others are not.
- Number of linkage groups = number of chromosomes.
Using recombination, what is found when mapping genes within linkage groups?
- maps are linear, so genes must be linearly arranged in chromosomes.
- each gene occupies a unique constant position (its locus).
What are copy number variants?
Short sequence of bases that occurs 2/3 times within a region of DNA at a single position in the genome.
What are indels?
Insertion or deletion, where it is unknown which one occurred.
What are inversions?
When regions of DNA have been switched around in a chromosome.
What are translocations?
Rearrangements of parts of non-homologous chromosomes.
What are transpositions?
When a chromosomal segment is transferred to a new position on the same chromosome.
When do chromosomal rearrangements occur and why?
During speciation as the species are becoming more likely to be infertile.
How do DNA sequences vary between individuals?
- changes in the amount of repetitive DNA
- changes in the number of times DNA sequences occur
- changes in the organisation of DNA
- changes in individual base pairs
- chromosomal rearrangements
How do individual DNA sequences vary?
They vary due to SNPs, Indels and STRs.
Why do SNPs occur?
Mostly due to DNA polymerase adding an incorrect base during replication.
Why do indels and STRs occur?
Mostly due to slippage and misaligning of DNA polymerase.
Where do VNTRs occur?
At thousands of loci in the genome.
What is the size of a VNTR?
Up to 25bp.
What is a tandem array?
Where a sequence occurs multiple times. The number of times the sequence is repeated in the tandem array varies between chromosomes of an individual and between other individuals.
How can VNTRs be detected?
Using a restriction enzyme that does not cut within the VNTR, digest the entire genome into fragments of different lengths. Separate by gel electrophoresis and use Southern blot. Band pattern produced for an individual is diagnostic.
How are VNTRs detected in population genetics?
Using PCR with primers for either side of the tandem array.
What are microsatellites (STRs)?
Commonly di/tri nucleotide repeats that occur due to slippage of DNA polymerase during replication.
How can STRs be identified?
Using PCR with primers for either side of the repeat and separate using capillary electrophoresis.
How does capillary electrophoresis separate STRs?
The sample is loaded at the top of the capillary tube. The rate of migration is detected by measuring the time it takes for fragments to reach the laser detector.
How are SNPs detected?
Using comparative DNA sequencing.
High numbers of SNPs can be genotypes using high throughput DNA sequencing.
What is a common SNP?
An SNP that is present in 5% of the population.
What is a haplotype?
Groups of alleles found on an individual chromosome.
Why do haplotypes occur?
Groups of loci that are close together are likely to share particular alleles because recombination will take a long time to shuffle the alleles.
What is the international Hapmap Project?
It describes the common patterns of human DNA sequence variation, focussing on the common SNPs.
It defines a minimum number of SNPs to analyse for whole genome genotyping.
It is used to find alleles associated with disease.
What so the gene pool?
The number of all the alleles present in a population.
What is a broad gene pool?
A gene pool that contains a wide range of alleles.
What is a shallow gene pool?
A gene pool where there is no particular alleles at a high frequency.
What are the limitations of the HWE?
- doesn’t consider assortative mating or natural selection
- doesn’t consider geographical isolation
- in HWE, it is genetically static (no migration/mutation/selection)
What does HWE predict?
Allele frequency and genotype frequency are the same in all populations and that allele frequency remains the same in the next generation.
What does heteroplasmic mean?
Cells have different copies of mtDNA.
What does homoplasmic mean?
Cells have the same mtDNA.
What is the size of the human mitochondrial genome?
16.5 kbp - which is relatively small.
Why is mtDNA easy to purify?
There are many mitochondria in each cell.
How is mtDNA inherited and why?
Maternally as the sperm contributes its nucleus but all the cytoplasm comes from the egg.
Where in mtDNA are mutations common?
In the D loop/control region, as this is hypervariable and contains the origin of replication. The D loop is non-coding.
Why is it thought that mtDNA sequences originated in Africa?
MtDNA variation is greatest in Africa, suggesting that more mutations have occurred there over a longer period of time.
What do shorter branches on a phylogenetic tree mean?
There are fewer base pair differences from the common ancestor. Longer branches mean more differences.
What is a complex trait?
A disease or other trait that shows variation in the phenotype due to interactions with the genome and the environment.
What does penetrance mean?
Defined as the number of individuals with a particular phenotype associated with an allele.
What does varying allele penetrance result in?
A phenotype not being observed in some individuals.
Give an example of full penetrance.
Mendel’s round and wrinkled peas were fully penetrant.
What is expressivity?
Defined as the range of expression of a particular phenotype associated with an allele, e.g. Fur colour in Siamese cats.
Give an example of incomplete penetrance.
The BRCA1 mutation which predisposes a woman to breast cancer but doesn’t guarantee the disease phenotype.
What are quantitative trait loci (QTLs)?
Interacting genes that contribute to continuous variation in polygenes.
How can QTLs be mapped?
Using extensive inbred lines or very large pedigree diagrams.
What is linkage equilibrium?
All combinations of alleles are just as likely to occur.
What is linkage disequilibrium?
Allele combinations are not equally as likely. When a new mutation occurs, it will tend to be passed on with all other alleles and mutations in the immediate chromosomal vicinity. It will take a long time for random combinations to be distributed by crossing over.
Where is linkage disequilibrium most commonly seen?
In alleles that are close together.
What is Affymetrix?
A high throughput sequencing technique that uses hybridisation stringency to detect single bp differences between the probe and genomic DNA.
What is Illumina?
A high throughput sequencing technique, using primer extension during replication to detect bp differences as the oligonucleotide stops just before the bp difference.
What is assortative mating?
Preferential mating between humans with similar characteristics.
Give an example of non-Mendelian inheritance.
- Leaf variegation.
- Small mutants in yeast.
Both occur because of variation in mtDNA.
