Linking chromosomes to genetics

1
Lecture 11 Genetics Wrap up
Readings From L9 and L10
Revision of Schedule and Overview where we have
been and where we are going Understand that
unlinked genes are recombined by independent
assortment understand that linked genes may be
recombined during crossing-over. parental types
recombinants. Use recombination data to map the
location of genes on chromosomes. linkage map,
map distance
 
Understand that experimental design is key in
quantitative genetics maternal effects,
environmental effects  Understand how linkage is
used to detect quantitative trait
loci RFLP Genome projects can provide useful
information to QTL studies Alcoholism - Mouse
QTLs application to humans Gene Expression
Studies Provide Real Time Information Microarrays
, Bee Brains
2
Revised Dixon Lecture Schedule

• 2/10 - Genetics Wrap up
• 2/13 - Genes and populations
• 2/15 - Microevolution
• 2/17 - Darwin
• 2/20 - Natural Selection
• 2/22 - Exam Review

• 2/23 (evening) - Exam 1
• 2/24 - Animal Behavior (chapter 51)
• 2/27 - Speciation and Systematics
• 3/1 - Human Evolution (readings TBA)

3
Review of Linkage and the Testcross

• Expectations of independent assortment vs.
  complete linkage
• Recombinant vs. Parental Types
• What is a test cross and why do you do it?
• Frequency of recombinants is related to physical
  distance between loci

4
Dihybrid Cross

• Independent Assortment - alleles at two loci
  segregate independently - if a gamete has A or a
  does not affect its probability of getting B or
  b.
• All four gamete genotypes (AB, ab, Ab, aB) are
  equally likely from an AaBb individual
• Complete linkage - alleles at the two loci are
  inherited together based on which parent they
  came from (see next slide).

5
AABB
X
aabb
Parental generation
Parental gametes
AB and ab
AaBb
F1 Generation
F1 gametes
AB and ab
This is what complete linkage looks like - NOT
TRUE for almost all genes
6
Testing for Linkage

• Cross two strains that differ at two loci
• Cross the F1 to the double homozygous recessive
  genotype (why?)
• This is called a test cross - look for the number
  of recombinant vs. parental phenotypes in the
  next generation

7
Recombinant vs. Parental Genotypes

• From two slides back
• Parents were AABB and aabb
• Parental genotypes (for gametes) are AB and ab
• Recombinant genotypes are Ab and aB

8
Drosophila melanogaster Meigen
wild-type female
ebony body, vestigial winged male
9
What Morgan actually saw - lots of parental
chromosomes, but also some recombinant phenotypes.
Fig. 15.5
10
An explanation for recombinant phenotypes in
terms of crossing-over between homologous
chromosomes.
Fig. 15.6
11
Recombination and Distance

• The greater the physical distance along the DNA
  between two loci, the greater the probability
  that a cross ever event will occur between them
• Two loci that are far enough apart that crossing
  occurs at least 50 of the time have complete
  independent assortment

12
The frequency of recombinant genotypes cannot be
gt 50

• If two loci are far enough apart that crossing
  over has a greater than 50 chance of occurring
  then double crossovers will turn recombinants
  back to parentals often enough to keep the
  proportion of each type equal

13
Back to Genetics of Complex Traits

• Last time - introduction to Quantitative Genetics
• Very important in agriculture and in lots of
  basic biology
• Next few slides contain some take home messages

14
Genetic Differences Within and Between Populations

• Within populations - genetic differences between
  individuals in the same population
• Between populations - genetic contribution to the
  difference in the mean
• One does not imply the other

15
Example

• All the individuals in pop A. have genotype XX,
  while all the individuals in pop. B have genotype
  xx. Heritability is zero in each population but
  the difference between has a genetic component.
• What is a reverse example?

16
Experimental Design is Crucial to Quantitative
Genetics

• Must be able to separate environmental and
  genetic factors
• Large samples and carefully controlled breeding
  are crucial

17
Studies of Human Genetics are very difficult

• Sample sizes are small
• Controlled crosses are impossible
• Control of environmental factors is usually
  impossible

18
Variance is also very important is assessing
information you receive in your daily life

• How would you assess this statement I dont
  believe smoking causes cancer because my uncle
  smoked heavily and lived to be 97

19
Modern Techniques

• Combine multi-gene approach with techniques used
  to identify genes
• Quantitative Trait Loci
• Gene Expression Studies

20
A simple example with Drosophila
Extreme phenotypes are crossed and then the
offspring are crossed. Crossing over is
suppressed using marker chromosomes.
Particular chromosomes can associated with the
trait
21
QTL mapping using RFLPs

• RFLP restriction fragment length polymorphism.
• Specific sites on the DNA where a nuclease
  cleaves the DNA

22
Use Crosses to Map QTLs

• Cross lines with different, extreme phenotypes
  (e.g. ethanol preferring and non-preferring mice)
• These lines also have different RFLP sites
• Continue crossing until you have a wide range of
  phenotypes and RFLP patterns
• Look for RFLPs that consistently match up to a
  phenotype (liking ethanol) - cosegregation

23
Alcoholism Genes

• Syntax bind protein - Stxbp1
• Neuropeptide Y - NPY
• Many other QTL can be located but more work needs
  to be done to ID the genes

24
Human QTLs?

• Cant do controlled crosses
• Can use family history - marriages of people from
  different backgrounds
• More commonly - use mice or rats as models - do
  QTL and then compare genes in the different
  genomes.

25
Sequenced Genomes

• Without a genome it would be sheer luck to
  identify a particular gene through QTL analysis
• Genomes are also used in microarray studies

26
(No Transcript)
27
Honeybees

• Change in behavior with age - very predictable
• Workers begin life in the hive (nurses)
• Later they work as foragers
• What happens to their brains when they change
  behaviors?

28
Microarrays of Bee Brains

• Use typical bees plus ones that are unusual (old
  nurses and young foragers)
• Found about 20 genes that have striking and
  consistent expression differences with age

29
Lecture 11 Genetics Wrap up
Readings From L9 and L10
Revision of Schedule and Overview where we have
been and where we are going Understand that
unlinked genes are recombined by independent
assortment understand that linked genes may be
recombined during crossing-over. parental types
recombinants. Use recombination data to map the
location of genes on chromosomes. linkage map,
map distance
 
Understand that experimental design is key in
quantitative genetics maternal effects,
environmental effects  Understand how linkage is
used to detect quantitative trait
loci RFLP Genome projects can provide useful
information to QTL studies Alcoholism - Mouse
QTLs application to humans Gene Expression
Studies Provide Real Time Information Microarrays
, Bee Brains