Polygenic traits

1.

Polygenic traits
1. Classic polygenic traits

2. In fact, all traits are controlled by multiple genes

 2.

The genetics of height

frequency

genotypes

frequency
short tall

genotypes
short tall

frequency
genotypes
short tall
 3.
Genetics of quantitive traits

body weigh height

gene 1
gene 2 phenotype(in pieces)
etc.

Quantitative traits are specified by the additive effect of genes:

„1 gene, 1 piece of phenotype” concept → Mendelian view
- Missing: interactions among genes!
 4.
Genetics of quantitive traits

Quantitative Trait Loci (QTL): regions of DNA that are associated with particular
phenotypic traits – these QTLS are often found in different chromosomes. Statistical analysis
is used to determine whether a particular gene (allele) contribute to a given phenotype.
 5.

The Polygenic Threshold Theory

Liability distribution
frequency

- + ++

migrénre való hajlam

migraine: no without aura with aura

 6.

Polygenic diseases
1. A disease is caused by the malfunction of several genes

2. A disease can be caused by the malfunction of anyone of the contributing genes

3. A disease is generally caused by the combined effect of genetic and environmental factors

Cancers, heart diseases, autoimmune diseases, diabetes, osteoporosis,

hypertension, obesity , atherosclerosis, depression, schizophrenia

Atherosclerosis Lung cancer Osteoporosis

 7.

How can monogenic traits exist?

A phenotype variant can be corresponded to a gene variant (allele), but it does not mean
that this gene would encode the specific phenotype, or that the specific allele alone would
encode the phenotype

1. The other genes are nonvariable, or their variability do not cause phenotype variation
2. The effect of one gene is strong (Hub gene)

3. The genes playing a role in the determination of a phenotype are physically linked,
therefore, their allele variants are also linked.
 8.
How can monogenic traits exist?
1. The other genes are functionally nonvariable, or their variability do not cause
phenotype variation

Genes responsible for the determination Gene 1

of a single phenotype allele A allele B

1A 1B
3 3
2 2
4 5 4 5
6 6
Individual 1 Individual 2

Haploid case
Phenotype
 9.
How can monogenic traits exist?
2. The effect of a gene is very strong

Gene 1
allele A allele B
Genes responsible for the
determination of a phenotype

1A 1A 1B 1B
3 3 2 3 2 3
2 2
4 5 4 5 4 5 4 5
6 6 6 6
Individual 1 Individual 2 Individual 3 Individual 4

Haploid case
Phenotype
 10.
How can monogenic traits exist?
3. The genes participating in the determination of a phenotype are located in close vicinity
in a chromosome, therefore the allele variants are physically linked, too

chromosome A

Individual 1 gene 1A gene 2A gene 3A gene 4A

Individual 2 gene 1B gene 2B gene 3B gene 4B

Haploid case

The frequency of recombination between genes is rare due to the short distance!
 11.

The relationship between

genes and phenotype
2 questions:

1. The fact: an allele of a single gene can unequivocally be corresponded to a

phenotype variant. Does it mean that this gene encode the given phenotype?

- In a strict sense NO, a gene can exert its effect in the context of other genes and
the whole body
- In a wider sense YES, but it is only a correlation

2. Are there many monogenic traits?

- NO, more and more monogenic traits turn out to be polygenic
 12.

Message

Monogenic traits are under the control of several genes, but in special
circumstances, some of them can appear as monogenic. More precisely,
the 1 gene, 1 phenotype relationship is never true, and the 1 allele, 1
phenotype variant relationship rarely occurs.
 13.
The Common Disease – Common Variant Hypothesis

The common variant hypothesis proposes that many familiar human maladies might be explained
by the inheritance of a relative small number of common gene variants..

Linked SNP INTERGENIC REGION

ouside the gen HEALTHY SICK
No effect on
proteins

Causal SNP
Inside genes
REGULATORY REGION
Regulatory SNP
amount of proteins gene
CODING REGION
Coding SNP
protein function
 14.
Common disease/Rare Variant
Hypothesis
David Goldstein

The common disease/common variant idea is largely wrong. A multitude of rare variants lie at the root of most
common diseases, being rigorously pruned away as soon as any starts to become widespread.