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Genes, Evolution and Development > Lecture 16 Complex traits > Flashcards

Lecture 16 Complex traits Flashcards

1
Q

Define a mendelian trait

A

Monogenic, predicatble mode of inheritance, high penetrance

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2
Q

Provide some examples of mendelian traits

A

Cystic fibrosis

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3
Q

Compare the penetrance of mendelian traits with complex traits

A

Mendelian traits have greater/higher penetrance

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4
Q

State the frequency of complex traits

A

600/1000

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5
Q

Define complex traits and describe the features of complex traits

A

Complex trait is multifactorial, controlled by more than one gene does not have a predictable mode of inheritance. Such traits are greatly influenced by the environment, often have a much lower penetrance than monogenic mendelian traits

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6
Q

Explain the difference between a complex trait and a mendelian trait

A

Mendelian traits are monogenic and follow a predictable pattern of inheritance

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7
Q

Explain the concept of heritability

A

Heritability is a measure of the proportion of variation between individuals for a particulat phenotype/ trait/disease that is due to genetic differences.
H2 = Vp/Ve

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8
Q

Explain how twin studies between MZ and DZ twins can be used to determine heritability of a particular trait

A

For a particular trait, say height difference. If there is greater similarity between two MZ twins for height than there is between fraternal twins, we can say that height has high heritability. This means that if two individuals are have different heights, this differences between individuals for height is due to genetic differences.

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9
Q

Explain linkage disequilibrium

A

Co inheritance of SNPs in a haplotype block is known as linkage disequilibrium. Linkage disequilibrium occurs when the frequency of 2 SNPs is different to the expected frequency.

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10
Q

Explain what is meant by linkage equilibrium

A

When the frequency of haplotypes from a block are at the expected frequency.

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11
Q

What is an SNP

A

SNP is a single nucleotide polymorphism.

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12
Q

Explain what a Genome wide study is and what is seeks to achieve

A

It is a study that typically has a case group and control group. Case group is bunch of diseased individuals. controls are healthy. The genotypes of the cases are screened and compared with controls genome to identify any SNPs. If there is a particular SNP that occurs more commonly in the diseased case group, this allele is a disease-associated SNP. And possession of this SNP increases your disease risk.

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13
Q

State the most common type of variation/mutation

A

SNPs as they occur every 1000 alleles.

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14
Q

Define frequency dependent selection

A

Frequency-dependent selection is an evolutionary process by which the fitness of a phenotype or genotype depends on the phenotype or genotype composition of a given population. … In negative frequency-dependent selection, the fitness of a phenotype or genotype decreases as it becomes more common.

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15
Q

Explain how haplotype blocks can be useful in simplifying genome wide association studies.

A

Haplotype blocks represent known regions in the genome where genetic variation is found among individuals. These blocks were mapped and identified in the HapMap project. So when looking for SNPs we look in these specific haplotype block regions!

(Genetic variation in the genome is organized into specific regions that are conserved throughout mammals, and occur among individuals)

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16
Q

Explain how we determine if a particular SNP is disease associated or not

A

Calculate the odds ratio for that allele, compared with the “normal” version.

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17
Q

Explain how the odds ratio can be calculated

A

[A]/[B] / [C]/[D]

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18
Q

Define haplotype

A

Haplotype is a set of closely linked SNPs (alleles) on the same chromosome.

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19
Q

A heritability value of 0.7 means what

A

Lets say we’re talking about height. A heritability of 0.7 = 70 .%. Does not mean that height is caused by 70% genes, 30% environment. It means that 70 % of the variation between individuals for height is due to genetic differences.

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20
Q

State the range for heritability values

A

Heritability estimates range in value from 0 to 1. If H = 1, then all variation in a population is due to differences or variation between genotypes (i.e., there is no environmentally caused variation). If H= 0, then there is no genetic variation for this trait.

21
Q

An odds ratio of greater than 1 means what?

A

if odds ratio > 1 then that allele is disease associated SNP

22
Q

What does an odds ratio for a particular allele of less than 1 tell you

A

If the odds ratio < 1, then that allele is proctive against disease

23
Q

Give some examples of complex trait diseases

A 
Crohns disease
Asthma
Type 1 and 2 diabetes
CVD
Neural tube defects like spina bifida 
Cleft lip palate 
Autism
Alzheimers
24
Q

Define continuous variation

A

Where a value for a trait lies on a spectrum and can be any value, eg height.

25
Q

Define discontinuous variation

A

Where a value for a trait fits into discrete, limited categories. Eg ABO blood groups. A persons blood group can only be A, B, AB or O.

26
Q

Explain the process of genotyping, what is it and how is it done

A

Genotyping is comparing the DNA sequences of 2 different people at a certain region and screening for variants (SNPs for example)

It is done by assays. Compare a persons dna sequence with a reference sequence.

27
Q

Describe the concept of variable expressivity

A

Variable expressivity refers to the various different signs and symptoms that 2 people with the same genetic condition can display.
Variable expressivity refers to the degree of severity of a conditon?

28
Q

Describe the concept of incomplete penetrance

A

Does the person with the genotype actually display the phenotype?

Penetrance refers to the likelihood that a clinical condition will occur when a particular genotype is present. A condition is said to show incomplete penetrance when some individuals who carry the pathogenic variant express the associated trait while others do not.

29
Q

Explain the difference between incomplete penetrance and incomplete dominance

A

Incomplete dominance is when 2 dominant alleles are expressed in the phenotype producing an intermediete,blended progeny which is a blend of the two dominant traits.eg red and white flowers make pink

30
Q

If everyone in a population has the same allele for a trait and shows little variation (differences) on that trait,what can we conclude is the heritability value for this trait.

A

H2 = 0. This is because for this trait, there is no genetic variation. Heritability is a property of the population not the individual. When the heritability of a trait is described, it reflects how much variability in the population is a consequence of genetic factors.

31
Q

Explain what a Genome wide association study aims to identify

A

-Genome-wide association studies examine SNPs across the genome
- Each study can look at hundreds or thousands of SNPs at the same time. Researchers use data from this type of study to pinpoint genes that may contribute to a person’s risk of developing a certain disease.
-

32
Q

Explain why studies such as genome wide association studies are now possible?

A

Due to completion of projects like The Human genome project 2015 and The HapMap project which provided a good set of research tools.
The tools include computerized databases that contain the reference human genome sequence, a map of human genetic variation and a set of new technologies that can quickly and accurately analyze whole-ge

33
Q

Explain how the International HapMap project/ Haplotype blocks are very useful in assisting Genome wide association studies to take place.

A

Haplotype blocks are conserved regions in the genome where genetic variation is typically found.
Having a Map of where most human genetic variation occurs means its is much easier to accurately analyze whole-genome samples for disease associated SNPs.

34
Q

Briefly summarise how genome wide association studies are conducted (refer to method/technology used)

A

1) Each person from the case and control groups have their entire genome/DNA is isolated from blood cells and placed on a tiny chip.
2) These chips are then scanned by machines that survey the entire genome for specifically selected SNPs.
3) If a certain SNP is at higher frequency in the case group than control group, then that is a Disease associated SNP.
4) This is confirmed by calculating the odds ratio for that SNP. An odds ratio of > 1 = Disease associated SNP.
5) Odds ratio of less than 1 = protective allele.

35
Q

Define variance

A

Variance is the spread of values around the mean of a standard distribution curve.

36
Q

Define mean (w.r.t the bell cuve)

A

This is the centre of the standard distribution bell curve.

37
Q

State the equation for Total phenotypic variance

A

Total phenotypic Variance = Genetic Variance + Environmental Variance.

38
Q

State the equation for Heriability (Broad sense)

A

h^2 = Genetic variance (additive and non additive) / Total phenotypic variance (Environmental + genetic ALLL)

39
Q

Clarify what a heritability value for 0 tell us? What can we conclude?

A

1) A H2 value of 0 means that for that particular trait in a specific population + environment there was no observed genetic variation at that specific loci in that population.
2) does not mean genes are irrelevant though!
3) In other populations or other environments, the trait might be heritable.

  • In general, the heritability of a trait is different in each population and in each set of environnents; it cannot be extrapolated from one population and set of environments to another.
40
Q

Explain how heritability can be estimated in humans using twin studies

A

???/

41
Q

Explain how linkage disequilibrium can be used in genome wide association studies to identfy genes involved in complex traits

A

1) Linkage disequilibrium (LD) is a property of SNPs in a haplotype block that describes the degree to which an allele of one SNP is inherited or correlated with an allele of another SNP within a population.
2) if 2 SNPs are occuring at a frequency different than expected, this is known as LD.
3) (roughly speaking, the’yre alleles that have not undergone genetic recombination over evolutionary time).
4) This is important in GWAS because LD allows us to get good coverage of the entire genome by genotyping only a small fraction of markers. Hence, one SNP can serve as a proxy (or “tag”) for other markers with which it is in high LD. The upside of LD is that it makes GWAS more efficient (or even possible with chip-based technologies).

42
Q

Give three reasons why disase associated alleles are still common?

A

1) Weak purifying selection - eg Huntingtons disease
2) Previously neutral/ advantageous alleles have become dangerous because of a change in environment (eg storing fat genes used to be helpful in period of starvation, but now with wide food abundance, it is dangerous!!)
3) disease causing alleles can be maintained at high frequency due to balancing selection (eg. heterozygote advantage maintains deleterious sickling allele)

43
Q

Narrow sense heritability calculation is

A

Additive genetic variance / Environmental variance + ALL genetic variance

44
Q

Broad sense heritability calculation is

A

Additive + non additive variance / Environmental variance + all genetic variance

45
Q

What is positional cloning of the disease gene.

A

Select candidate genes in the region of the chromosome. Search for disease associated SNPs in each gene.

46
Q

What is the puprpose of a gene chip

A

narrows down the search for the gene causing a disease. Gene chip contains millions of SNPs.

47
Q

Explain the 3 stages involved in identifying the gene responsbile for a disease

A

1) Pedigree analysis to identify type of mutation
2) Linkage analysis using DNA markers (not phenotypic markers as this is v limited)
3) Positional cloning to identify candidate genes/regions to hone in on the final gene responsible for that disease (final step)

48
Q

State 2 features of DNA markers

A
  • Must be easy to assay (easy to distinguish from other alleles)
  • Must be polymorphic
49
Q

What is linkage analysis using DNA markers

A

This is where individuals who have a disease have DNA screened to see if they have any disease associated SNPs.

Normal linkage mapping is carried out to see if the disease associated SNP is
??? not sure tbj

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