The Genetic Basis of Complex Inheritance

1

• 15
• The Genetic Basis of Complex Inheritance

2
Multifactorial Traits

• Multifactorial traits are determined by multiple
  genetic and environmental factors acting together
• Multifactorial complex traits quantitative
  traits
• Most traits that vary in the population,
  including common human diseases with the genetic
  component, are complex traits
• Genetic architecture of a complex trait
  specific effects and combined interactions of all
  genetic and environmental factors

3
Quantitative Inheritance

• Quantitative traits phenotypes differ in
  quantity rather than type (such as height)
• In a genetically heterogeneous population,
  genotypes are formed by segregation and
  recombination
• Variation in genotype can be eliminated by
  studying inbred lines homozygous for most
  genes, or F1 progeny of inbred lines uniformly
  heterozygous
• Complete elimination of environmental variation
  is impossible

4
Quantitative Inheritance

• Continuous traits continuous gradation from one
  phenotype to the next (height)
• Categorical traits phenotype is determined by
  counting (hens eggs)
• Threshold traits only two, or a few phenotypic
  classes, but their inheritance is determined by
  multiple genes and environment (adult-onset
  diabetes)

5
Multiple gene hypothesis range of phenotypes
can be accounted for by cumulative effect of many
alleles. Polygenes Additive allele nonadditive
allele 1 phenotypic traits can be measured eg.
weight or height 2 two or more loci (genes)
could account for phenotype in an additive or
cumulative way 3 each loci may be occupied by an
additive allele, which contributes a constant
amount to the phenotype, or a nonadditive allele
which does not 4 The contribution by each allele
may be small and is approx equal 5 together the
alleles contribute to a single phenotypic
character with substantial variation.
6
(No Transcript)
7
Distributions

• Distribution of a trait in a population
  proportion of individuals that have each of the
  possible phenotypes
• Mean peak of distribution
• ?x ?xi /N
• Variance spread of distribution estimated by
  squared deviation from the mean s2?(xi - ?x
  )2/N-1
• Standard deviation square root of the variance
• s v s2

8
Normal Distribution

• Normal distribution symmetrical curve produced
  by data in which half points are above and half
  points are below mean
• 68 of a population have a phenotype within one
  standard deviation (s) of the mean
• 95 - within 2 s
• 99.7 - within 3 s
• The distribution of a trait in a population
  implies nothing about its inheritance

9
Fig. 15.5
10
Phenotypic Variation

• Variation of a trait can be separated into
  genetic and environmental components
• Genotypic variance sg2 variation in phenotype
  caused by differences in genotype
• Environmental variance se2 variation in
  phenotype caused by environment
• Total variance sp2 combined effects of
  genotypic and environmental variance
• sp2 sg2 ?e2

2 cov ge
11
Analysis of a quant trait Tomato fruit P1
ave6oz P2 ave18oz
12
Phenotypic Variation

• Genotype and environment can interact or they can
  be associated
• Genotype-environment (G-E) interaction
  environmental effects on phenotype differ
  according to genotype
• Genotype-by-sex interaction same genotype
  produces different phenotype in males and females
  (distribution of height among women and men)

13
Genetic Variation

• Genotype-environment (G-E) association certain
  genotypes are preferentially associated with
  certain environments
• There is no genotypic variance in a genetically
  homogeneous population sg2 0
• When the number of genes affecting a quantitative
  trait is not too large, the number, n, of genes
  contributing to the trait is
• n D2/8sg2
• D difference between parental strains

14
Fig. 15.10
15
Broad-Sense Heritability

• Broad-sense heritability (H2) includes all
  genetic effects combined
• H2 sg2 / sp2 sg2 / sg2 se2
• Knowledge of heritability is useful in plant and
  animal breeding because it can be used to predict
  the magnitude and speed of population improvement

16
Heritability Twin Studies

• Twin studies are often used to assess genetic
  effects on variation in a trait
• Identical twins arise from the splitting of a
  single fertilized egg genetically identical
• Fraternal twins arise from two fertilized eggs
  only half of the genes are identical
• Theoretically, the variance between identical
  twins would be equivalent to se2 , and between
  fraternal twins - sg2/2 se2

17
Heritability Twin Studies

• Potential sources of error in twin studies of
  heritability
• Genotype-environment interaction increases the
  variance in fraternal twins but not identical
  twins
• Frequent sharing of embryonic membranes by
  identical twins creates similar intrauterine
  environment
• Greater similarity in treatment of identical
  twins results in decreased environmental variance
• Different sexes can occur in fraternal but not
  identical twins

18
Narrow-Sense Heritability

• Narrow-sense heritability (h2) proportion of
  the variance in phenotype that is transmissible
  from parents to offspring. The genetic variance
  can be split into both additive and dominant
  alleles.
• h2 sg2 / sp2 sg2 / sa2 sd2 se2
• Narrow-sense heritability can be used to predict
  changes in the population mean in with individual
  selection
• h2 (M - M)/(M - M)
• In general, h2 lt H2 . They are equal only when
  the alleles affecting the trait are additive in
  their effects heterozygous phenotype is exactly
  intermediate between homozygous dominant and
  recessive

19
Artificial Selection

• Artificial selection managed evolution the
  practice of selecting a group of organisms from a
  population to become the parents of the next
  generation
• h2 is usually the most important in artificial
  selection
• Individual selection each member of the
  population to be selected is evaluated according
  to its individual phenotype
• Truncation point arbitrary level of phenotype
  that determines which individuals will be used
  for breeding purposes

20
Artificial Selection

• There are limits to the improvement that can be
  achieved by artificial selection
• Selection limit at which successive generations
  show no further improvement can be reached
  because natural selection counteracts artificial
  selection due to indirect harmful effects of
  selected traits (weight at birth versus
  viability)
• Correlated response effect of selection for one
  trait on a non-selected trait (number of eggs and
  their size)

21
Inbreeding

• Inbreeding can have harmful effects
• Inbreeding depression decrease in fitness due
  to harmful recessive alleles which become
  homozygous
• Heterosis hybrid vigor refers to superior
  fitness of heterozygote often used in
  agricultural crop production

Fig. 15.14
22
Correlation Between Relatives

• Genetic variation is revealed by correlations
  between relatives
• Covariance (Cov), the tendency for traits to vary
  together, is Cov(x,y)?fi(xi - ?x )(yi - ?y )/N-1
• Correlation coefficient (r) statistical
  evaluation of paired data (pairs of parents,
  twins, parent and offspring)
• r Cov(x,y)/sxsy
• Covariance and correlation coefficient are
  important in heritability estimates

23
Correlation Between Relatives

• Correlation coefficient of a trait between
  relatives is related to the narrow- or
  broad-sense heritability

24
Threshold Traits Heritability

• Liability quantitative trait that presents a
  genetic risk for a threshold trait
• Individuals with a liability above threshold
  develop the trait
• The risk of manifesting a threshold trait has H2
  and h2 that cannot be estimated directly, but can
  be inferred from the incidents of the trait among
  individuals and their relatives

25
Threshold Traits Heritability

• Many congenital abnormalities are inherited as
  threshold traits
• Heritability analyses can be used to determine
  recurrence risks
• Theoretical curves show incidence, type of
  inheritance and risk among first-degree relatives
  of an affected individual

26
Multifactorial Disorders

• Most common disorders in human families are
  multifactorial
• Pedigree studies of genetic polymorphisms
• are used to map loci for quantitative traits
• Quantitative trait locus (QTL) gene that
  affects a quantitative trait
• Simple tandem repeat polymorphisms (STRPs) are
  used to locate QTLs
• Candidate gene gene for which there is some a
  priori basis for suspecting that it affects the
  trait