introduction to genetics lecture 1 overview. genetics for statisticians msc course duration:...
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Introduction to Genetics
Lecture 1 Overview
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Genetics for Statisticians
MSc Course
Duration: 18Hours, 6 x 3hour sessions
Dates: Thursday 23rd May: 4:30-8:15Thursday 30th May: 4:30-8:15Thursday 6th June: 4:30-8:15
Thursday 13th June: 4:30-8:15Thursday 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
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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
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Video: ABC News: All in the family: Mixed race twins
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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
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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
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A Few Basic Genetic Terms
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Many Genetic Traits Have Dominant and Recessive Forms
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Basic Concepts of Heredity (2)
Homozygous condition: identical alleles
Heterozygous condition: different alleles
Dominant allele• Effect masks recessive allele paired with it
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Basic Concepts of Heredity (3)
Genetic representations• Homozygous dominant (AA)• Homozygous recessive (aa)• Heterozygous (Aa)
Genotype• Inherited alleles
Phenotype • Observable functional or physical traits
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Genotype and Phenotype Compared
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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
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One Chromosome, One Copy of a Gene
Monohybrid cross• Learn more about genotypes
Segregation• Pairs of alleles separated during gamete
formation
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The Trait Called a Chin Fissure Arises from One Allele of a Gene
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Animation: Chromosome segregation
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Each Pair of Gene Alleles Is Separated and Two Alleles End Up in Different Gametes
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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
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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
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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
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Making a Punnett Square Is One Way to Determine Likely Outcome of Genetic Cross
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Different Genetic Results Possible in Second
Generation after Monohybrid Mating
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Use Multiplication to Figure the Probability of the Inheritance of Alleles
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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
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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
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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
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Independent Assortment: Chromosomes Moved at Random into Forming Gametes
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Fig. 19-8, p. 378
One of two possible alignments The only other possible alignment
a Initial chromo- some alignments (at metaphase I):
b The resulting alignments at metaphase II:
c Possible combinations of alleles in gametes: AB ab Ab aB
Stepped Art
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Tracking Two Traits Shows the Results of Independent Assortment
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Fig. 19-9, p. 379
CcDd CcDdmeiosis,
gamete formationmeiosis,
gamete formation
1/4 CD
1/4 Cd
1/4 cD
1/4 cd
1/4 CD
1/16 CCDD
1/16 CCDd
1/16 CcDD
1/16 CcDd
1/4 Cd
1/16 CCDd
1/16 CCdd
1/16 CcDd
1/16 Ccdd
1/4 cD
1/16 CcDD
1/16 CcDd
1/16 ccDD
1/16 ccDd
1/4 cd
1/16 CcDd
1/16 Ccdd
1/16 ccDd
1/16 ccdd
Adding up the combinations possible:
9/16 or 9 chin fissure, dimples3/16 or 3 chin fissure, no dimples
3/16 or 3 smooth chin, dimples1/16 or 1 smooth chin, no dimples
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Probability Rules Apply to Independent Assortment
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19.5 Single Genes, Varying Effects
Some traits have clearly dominant and recessive forms
For most traits, however, the story is not so simple
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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
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Single Genetic Change Leads to Many Physical Effects of Sickle-Cell Anemia
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Fig. 19-11a, p. 380
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Fig. 19-11b, p. 380
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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
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There Are Several Possible Allele Combinations for ABO Blood Types
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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
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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
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People with Polydactyly Have Extra Digits on Their Hands or Feet
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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
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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
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Eye Color Is Just One of Many Human Polygenic Traits
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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
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“Tongue-Roller” Trait Is Due to a Dominant Allele