Download 1. Genetics

Introduction to Genetics
Lecture 1 Overview
Genetics for Statisticians
MSc Course
Duration: 18Hours, 6 x 3hour sessions
Dates:
Thursday 23rd May: 4:30-8:15
Thursday 30th May: 4:30-8:15
Thursday 6th June: 4:30-8:15
Thursday 13th June: 4:30-8:15
Thursday 20th June: 4:30-8:15
Presenters:
Dr Samuel Murray BSc, Hons , PhD, MRCP
Dr Fotios Siannis PhD
Session Titles:
1. Genetics: The basics
2. Analytical methodologies and global standardisation issues
[measures, cutoffs, ROC, EQA, sens/spec, reproducibility and requirements]
3. Biomarkers and their surrogates: integration into clinical medicine
[prog/pred, designs – old v new v novel, case control, Harvey W Equilb, endpoints-RR, cross over, censorship]
4. Practical application and interpretation of large data sets: ‘Omics’
[design, interpretation, validation, algorithms]
5. Spotting methodological flaws, limitations of study design, multiplicity
[p53, OncoDx, missing data, understanding the question, MA, post hoc]
www.biology-resources.com/genetics
Impacts, Issues: The Color of Skin
 Skin color comes from the pigment melanin
• Produced by melanocytes in skin cells
• More than 100 genes directly or indirectly
influence amount of melanin in an individual’s skin
• Lead to many variations in skin color
Video: ABC News: All in the family:
Mixed race twins
19.1 Basic Concepts of Heredity
 Genes provide the instructions for all human
traits, including physical features and how body
parts function
 Each person inherits a particular mix of maternal
and paternal genes
Basic Concepts of Heredity (1)
 Genes
• Humans have ~21,500
• Chemical instructions for building proteins
• Locus: specific location on a chromosome
 Diploid cells contain two copies of each gene on
pairs of homologous chromosomes
 Allele: each version of a gene
A Few Basic Genetic Terms
Many Genetic Traits Have Dominant and
Recessive Forms
Basic Concepts of Heredity (2)
 Homozygous condition: identical alleles
 Heterozygous condition: different alleles
 Dominant allele
• Effect masks recessive allele paired with it
Basic Concepts of Heredity (3)
 Genetic representations
• Homozygous dominant (AA)
• Homozygous recessive (aa)
• Heterozygous (Aa)
 Genotype
• Inherited alleles
 Phenotype
• Observable functional or physical traits
Genotype and Phenotype Compared
19.2 One Chromosome, One Copy
of a Gene
 We inherit pairs of a genes (alleles) on pairs of
chromosomes, but a gamete receives only one
gene from each pair
One Chromosome, One Copy of a Gene
 Monohybrid cross
• Learn more about genotypes
 Segregation
• Pairs of alleles separated during gamete
formation
The Trait Called a Chin Fissure Arises
from One Allele of a Gene
Animation: Chromosome segregation
Each Pair of Gene Alleles Is Separated and
Two Alleles End Up in Different Gametes
19.3 Genetic Tools: Testcrosses and
Probability
 When potential parents are concerned about
passing a harmful trait to a child, genetic
counselors must try to predict the likely outcome
of the mating
Probability
 Measure of the chance that some particular
outcome will occur
 Factor in the inheritance of single-gene traits
 Cross CC x cc
• All of the offspring will be heterozygous, Cc
 Cross Cc x Cc
• ¼ CC, ½ Cc, and ¼ cc
A Punnett Square Can Be Used to Predict
the Result of a Genetic Cross
 Punnett square
• Grid used to determine possible outcomes of
genetic crosses
• Rules of probability apply because fertilization is
a chance event
• Possibility can be expressed mathematically, e.g.,
between 0% and 100%
 Most probable outcome does not have to occur
 In a given situation, probability does not change
Making a Punnett Square Is One Way to
Determine Likely Outcome of Genetic Cross
Different Genetic Results Possible in Second
Generation after Monohybrid Mating
Use Multiplication to Figure the
Probability of the Inheritance of Alleles
A Testcross Also Can Reveal Genotypes
 Testcross
• Learn the genotype of a (nonhuman) organism
• Cross organism with homozygous recessive
organism (aa)
• If all offspring are Aa, parent was probably AA
• If some of the offspring have the dominant trait and
some have the recessive trait, parent was Aa
19.4 How Genes for Different Traits Are
Sorted into Gametes
 When we consider more than one trait, we see
that the gene for each trait is inherited
independently of the gene of other traits
How Genes for Different Traits Are
Sorted into Gametes
 Independent assortment
• Occurs during meiosis
• A given chromosome and its genes move
randomly into gametes
• Metaphase I
• Metaphase II
 Crosses between individuals heterozygous for
two traits yields sixteen different gamete unions
• Probability displayed using a Punnett square
Independent Assortment: Chromosomes
Moved at Random into Forming Gametes
One of two possible alignments
The only other possible alignment
a Initial chromosome alignments
(at metaphase I):
b The resulting
alignments at
metaphase II:
c Possible
combinations
of alleles in
gametes:
AB
ab
Ab
aB
Stepped Art
Fig. 19-8, p. 378
Tracking Two Traits Shows the Results
of Independent Assortment
CcDd
meiosis,
gamete formation
1/4
CD
CcDd
meiosis,
gamete formation
1/4
Cd
1/4
cD
1/4
cd
1/4 1/16
1/16
1/16 1/16
CD CCDD CCDd CcDD CcDd
1/4 1/16 1/16 1/16 1/16
Cd CCDd CCdd CcDd Ccdd
1/4 1/16 1/16 1/16 1/16
cD CcDD CcDd ccDD ccDd
1/4 1/16
1/16
1/16
cd CcDd Ccdd ccDd
Adding up the combinations possible:
9/16 or 9 chin fissure, dimples
3/16 or 3 chin fissure, no dimples
3/16 or 3 smooth chin, dimples
1/16 or 1 smooth chin, no dimples
1/16
ccdd
Fig. 19-9, p. 379
Probability Rules Apply to Independent
Assortment
19.5 Single Genes, Varying Effects
 Some traits have clearly dominant and recessive
forms
 For most traits, however, the story is not so
simple
One Gene May Affect Several Traits
 Pleiotropy
• Wide-ranging effect of one gene
 Sickle-cell anemia
• One amino acid substitution in hemoglobin
• Val instead of glu
• Pleiotropic effects
• Treatments
Single Genetic Change Leads to Many
Physical Effects of Sickle-Cell Anemia
Fig. 19-11a, p. 380
Fig. 19-11b, p. 380
In Codominance, More Than One Allele of
a Gene Is Expressed
 Codominance
• Heterozygous for a trait, but both alleles are
expressed
• Example: alleles for blood type determine presence
or absence of polysaccharides on surface of red
blood cells
• IA and IB; codominant when paired with each other
 Multiple allele system
• A gene that has three or more alleles
There Are Several Possible Allele
Combinations for ABO Blood Types
19.6 Other Gene Effects and Interactions
 Many phenotypes, such as eye color, can’t be
predicted with certainty
 Biologists have uncovered several underlying
causes for these variations
Other Gene Effects and Interactions
 Penetrance
• Probability that someone who inherits an allele
will have the phenotype associated with it
 Cystic fibrosis
• Homozygous recessive
• 100% penetrant
 Polydactyly
• Dominant allele for extra digits
• Incompletely penetrant
People with Polydactyly Have Extra
Digits on Their Hands or Feet
Polygenic Traits Come from Several
Genes Combined (1)
 Polygenic traits
• Combined expression of several genes
• Skin and eye color; many variations due to the
amount and distribution of melanin
 Continuous variation
• Populations show a range of continuous
differences
• Most evident in traits that can be measured, e.g.,
height
Polygenic Traits Come from Several
Genes Combined (2)
 Multifactorial trait
• Phenotypes shaped by more than one gene and
affected by the environment, e.g., height
Eye Color Is Just One of Many Human
Polygenic Traits
The Environment Can Affect Phenotypes
 Height
• Diet low in protein
• Disease or injury that prevents the normal release
of growth hormone
 Skin color
• Tanning
 Good lifestyle choices
• May limit the chances that a harmful gene(s) will
be expressed
“Tongue-Roller” Trait Is Due to a
Dominant Allele