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12/15/2011
1
Genetic
Mendle’s law
Patterns of Inheritance
• Mendel’s Laws
• Variations on Mendel’s Laws
• The Chromosomal Basis of Inheritance
• Sex Chromosomes and Sex-linked Genes
12/15/2011
2
The Field of Genetics has Ancient Roots
• Hippocrates (father of medicine): particles from every part of
the body travel to eggs
and sperm to be passed on
• Aristotle (philosopher): ‘potential’ rather than particles to
produce body features
• 19th century biologists: blending- mom and dad’s traits blend
like blue and yellow paint
Hippocrates Aristotle
Experimental Genetics Began in an Abbey Garden
• Modern genetics began in 1860s
• Gregor Mendel (monk in what was then Austria- now Czech
Republic)
• Parents pass on discrete, heritable factors (1866)
• Heritable factors retain their individuality for generations (no
blending)
• Studied garden peas
12/15/2011
3
• In a typical breeding experiment
– Mendel mated two different, true-breeding varieties, a process
called hybridization
• The true-breeding parents
– Are called the P generation
• The hybrid offspring of the P generation
– Are called the F1 generation
– F2 generation comes next
Experimental Genetics Began in an Abbey Garden
• Cross: pollinating a flower of one variety with the pollen of
another variety
Mendel chose to work with peas:
– Because they are available in many varieties
– Because he could strictly control which plants mated with
which
– Because he could easily start his experiments with varieties
that were “true-breeding”
12/15/2011
4
Some genetic vocabulary
Character: a heritable feature, such as flower color
Trait: a variant of a character, such as purple or white flowers
Gene: a discrete unit of hereditary information consisting of a
specific
DNA (nucleotide) sequence on a chromosome
Allele: alternative version of a gene
Mendel’s Law of Segregation Describes the Inheritance of a
Single Characteristic
Performed monohybrid crosses (only 1 trait differs between the
varieties)
• When Mendel crossed contrasting, true-breeding white and
purple
flowered pea plants
» All of the offspring were purple!!!
Mendel discovered:
A ratio of about three to one (3:1)
purple to white flowers,
in the F2 generation
When Mendel crossed the F1 plants –
Many of the plants had
purple flowers, but some
had white flowers
12/15/2011
5
Mendel’s Law of Segregation Describes the Inheritance of a
Single Characteristic
Mendel developed a hypothesis to explain the 3:1 inheritance
pattern that he observed
among the F2 offspring
Four Parts:
1. First, alternative versions of genes account for variations in
inherited characters
which are now called alleles
Allele for purple flowers
Locus for flower-color gene
Homologous
pair of
chromosomes
Allele for white flowers
Mendel’s Model for Inheritance
Four Parts:
1. First, alternative versions of genes account for variations in
inherited characters
which are now called alleles
2. Second, for each character an organism inherits two alleles,
one from each parent.
These alleles may be the same or different!
Locus for flower-color gene
12/15/2011
6
Mendel’s Model for Inheritance
Four Parts:
1. First, alternative versions of genes account for variations in
inherited characters
which are now called alleles
2. Second, for each character an organism inherits two alleles,
one from each parent.
These alleles may be the same or different!
Locus for flower-color gene
3. Third, if the two alleles at a locus differ then one, the
dominant allele, determines the
organism’s appearance.
The other allele, the recessive allele, has no noticeable effect
on the organism’s appearance
4. Fourth, A sperm or egg carries only one allele for each
inherited trait because
allele pairs separate (segregate) from each other during the
production of gametes
Does Mendel’s segregation model account for the 3:1 ratio he
observed
in the F2 generation of his numerous crosses?
We can answer this question using a Punnett square
12/15/2011
7
The Punnet Square
• A very convenient tool used in genetics.
• Steps:
– 1. Determine the parents gametes.
• This may be the most important step.
– 2. Match the gametes, and form possible offspring.
– 3. Determine the chances of each type of offspring.
A basic Punnet square:
• Notice that the mother and father
are both heterozygous.
• If the dominant sperm fertilizes
the dominant egg, then the
offspring would be TT.
– There is a 25% chance of this
occurring.
– 1 out of 4 will be this.
12/15/2011
8
Scientists use a “test cross” if they don’t know what the
genotype of an individual is.
• What is the:
– Phenotype of a purple pea plant?
– Phenotype of a white pea plant?
– Genotype of a white pea plant?
– Genotype of a purple pea plant?
• How can you find out the unknown genotype of an individual?
• You would want to breed a “known” genotype against your
“unknown.”
– The offspring will tell you what the “unknown” is.
12/15/2011
9
Not Just Flower Color!
Vocabulary – Enough Already!
• Punnett square: used to determine genotypic and phenotypic
frequencies
• Phenotype: an organism’s expressed traits (outward
appearance)
• Genotype: an organism’s genetic makeup (gene combinations)
12/15/2011
10
An organism that is homozygous for a particular gene:
– Has a pair of identical alleles for that gene
– Exhibits true-breeding
An organism that is heterozygous for a particular gene:
– Has a pair of alleles that are different for that gene
Homologous Chromosomes Bear the Two Alleles for Each
Characteristic
Remember:
Alleles (alternative forms) of a gene reside at the same locus
on homologous chromosomes
– Homozygous: both alleles match (either dominant or
recessive)
– Heterozygous: one allele is dominant, one is recessive
12/15/2011
11
Albinism
Failure to synthesize the pigment melanin
From: Introduction to Genetic Analysis, 8th Ed. Griffiths et al.
The Punnet Square
• A very convenient tool used in genetics.
• Steps:
– 1. Determine the parents gametes.
• This may be the most important step.
– 2. Match the gametes, and form possible offspring.
– 3. Determine the chances of each type of offspring.
12/15/2011
12
A basic Punnet square:
• Notice that the mother and father
are both heterozygous.
• If the dominant sperm fertilizes
the dominant egg, then the
offspring would be TT.
– There is a 25% chance of this
occurring.
– 1 out of 4 will be this.
Scientists use a “test cross” if they don’t know what the
genotype of an individual is.
• What is the:
– Phenotype of a purple pea plant?
– Phenotype of a white pea plant?
– Genotype of a white pea plant?
– Genotype of a purple pea plant?
• How can you find out the unknown genotype of an individual?
• You would want to breed a “known” genotype against your
“unknown.”
– The offspring will tell you what the “unknown” is.
12/15/2011
13
Independent Assortment is Revealed by Tracking Two
Characteristics at Once
• Dihybrid cross: cross individuals differing in two
characteristics
• Mendel crossed peas with round, yellow seeds (dominant
traits) and peas with wrinkled, green
seeds (recessive traits)
• Determined that traits were passed independent of each other
(got yellow, wrinkled offspring, for
example)
• Law of independent assortment: each pair of alleles segregates
independently of the other pairs of
alleles during gamete formation
Putting Mendel’s Laws on the Chromosomes!
12/15/2011
14
Putting Mendel’s Laws on the Chromosomes!
Putting Mendel’s Laws on the Chromosomes!
12/15/2011
15
Putting Mendel’s Laws on the Chromosomes!
Putting Mendel’s Laws on the Chromosomes!
12/15/2011
16
Putting Mendel’s Laws on the Chromosomes!
Independent Assortment of Two Genes in the Labrador
Retriever
PRA = Progressive Retinal Atrophy
• Coat color and ‘normal’ vision controlled by separate genes
• Blanks in the figure can represent either dominate or recessive
alleles
• Yellow labs have coat color controlled by different gene
altogether!
12/15/2011
17
In many cases, the genotype is not immediately obvious
Geneticists Use The Testcross to Determine Unknown
Genotypes
• A testcross allows one to determine the genotype of an
organism with the dominant
phenotype but unknown genotype
• Crosses an individual with the dominant phenotype with an
individual that is homozygous
recessive for a trait
Offspring phenotypes
tell you the unknown
genotype
Mendel’s Laws Reflect the Rules of Probability
• Event certain to take place: 1; event certain NOT to take
place: 0
• Probabilities of all outcomes must add to 1
• Rule of multiplication: multiply probability of two
independent events happening
(flipping a coin twice, for example)
12/15/2011
18
Mendel’s Laws Reflect the Rules of Probability
• What about genetics?
• Trihybrid cross: what’s the probability of getting homozygous
recessive at all 3
locations (AaBbCc x AaBbCc)?
– Probability aa: ¼
– Probability bb: ¼
– Probability cc: ¼
Probability aabbcc: ¼ x ¼ x ¼ = 1/64
12/15/2011
19
Genetics Traits in Humans Can be Tracked Through Family
Pedigrees
• Many traits simple Mendelian traits:
– Freckles
– Widow’s peak
– Free earlobes
• Pedigree: family tree
• Square: male, circle: female
female
male
male with trait
female with trait
Genetics Traits in Humans Can be Tracked Through Family
Pedigrees
Pedigree showing the inheritance of deafness in a family from
Martha’s Vineyard
12/15/2011
20
Many Inherited Disorders in Humans are Controlled by a Single
Gene
• Recessive disorders:
– Most human genetic disorders
– Most common lethal disorder: cystic fibrosis (most common
among Caucasians)
– Rate of disorders increases with inbreeding
• Dominant disorders:
– Most are non-lethal (dwarfism, extra fingers and toes)
– Lethal examples: Huntington’s Diesase
Many Inherited Disorders in Humans are Controlled by a Single
Gene
• Recessive disorders:
– Most human genetic disorders
– Most common lethal disorder: cystic fibrosis (most common
among Caucasians)
– Rate of disorders increases with inbreeding
• Dominant disorders:
– Most are non-lethal (dwarfism, webbed fingers and toes, extra
fingers and toes)
– Lethal examples: Huntington’s Diesase
12/15/2011
21
Concept Check
A man and a woman who are both carriers of the Martha’s
Vineyard deafness
allele have had three children who are not deaf. If the couple
has a fourth child,
what is the probability that the child will be deaf?
1/4
Variations on Mendel’s Laws – i.e. Complications,
Complications!
1. Incomplete Dominance
2. Multiple Alleles for a single gene
3. Pleiotropy – some genes have multiple phenotypic
characteristics
4. Polygenic Inheritance – additive effects of 2 or more genes
(Non-Mendelian Genetics)
12/15/2011
22
Incomplete Dominance in Snapdragons and Carnations
Or, what if Mendel had studied snapdragons?!
• Complete dominance: dominant allele always expressed,
recessive allele expressed in
homozygous condition
• Incomplete dominance: heterozygote is intermediate to
dominant and recessive alleles
• Classic example: snapdragons/carnations
Incomplete dominance results in intermediate phenotypes
+ =
Incomplete Dominance in Snapdragons and Carnations
12/15/2011
23
Michael Brown Joseph Goldstein
Nobel Prize (1985)
Physiology or Medicine
Cholesterol uptake lead to the discovery of
Receptor Mediated Endocytosis
Famial Hypercholesterolemia: Genetic Disorder
Death
homozygotes ~ 10 to teens
heterozygotes < 50
Exceptions to Mendel’s Laws - Incomplete Dominance
Familial Hypercholesterolemia
12/15/2011
24
Variations on Mendel’s Laws – i.e. Complications,
Complications!
1. Incomplete Dominance
2. Multiple Alleles for a single gene
3. Pleiotropy – some genes have multiple phenotypic
characteristics
4. Polygenic Inheritance – additive effects of 2 or more genes
(Non-Mendelian Genetics)
Many Genes Have More Than Two Alleles in the Population
• Why only two alleles? Many genes have more
• Example: blood types
• A and B dominant, O recessive
12/15/2011
25
Variations on Mendel’s Laws – i.e. Complications,
Complications!
1. Incomplete Dominance
2. Multiple Alleles for a single gene
3. Pleiotropy – some genes have multiple phenotypic
characteristics
4. Polygenic Inheritance – additive effects of 2 or more genes
(Non-Mendelian Genetics)
A Single Gene May Affect Many Phenotypic Characteristics
Pleiotropy: gene influences multiple characteristics
• Example: sickle-cell disease
• Causes red blood cells to become misshapen (sickle shaped) in
low oxygen environments
• Heterozygote usually doesn’t suffer much, but has resistance
to malaria (homozygous
recessive is sensitive to malaria)
12/15/2011
26
Pleiotropy: gene influences multiple characteristics
• Example: sickle-cell disease
Variations on Mendel’s Laws – i.e. Complications,
Complications!
1. Incomplete Dominance
2. Multiple Alleles for a single gene
3. Pleiotropy – some genes have multiple phenotypic
characteristics
4. Polygenic Inheritance – additive effects of 2 or more genes
(Non-Mendelian Genetics)
12/15/2011
27
Polygenic Inheritance of Skin Color
Consider:
• Hypothetical example (at least three genes for skin color)
• Three (at least!) ‘dark’ skin alleles for each gene
• A, B, C incompletely dominant to a, b, c
Polygenic inheritance: Two or more genes influence a
single phenotype
Genes and the Environment
Temperature
Soil pH
‘Nature vs Nurture’
Acid Neutral/Alkaline
http://www.tradenets.com/cats/sirulean.htm
12/15/2011
28
Genes and the Environment
‘Nature vs Nurture’
Exercise and Sun Exposure
• Many human phenotypes are influenced by both genes and
environment:
– Risk of heart disease
– Risk of cancer
– Susceptibility to alcoholism and schizophrenia
– In addition to genes, sun affects skin color
CITM 501 Spring/Summer 2014
Homework Assignment 5
Due Month #, 2014 @5 PM via Bb
Refer to the models at the end of this document to answer the fo
llowing questions.
Solve model A adding answer and sensitivity analysis reports to
your output. Answer the
following questions based on the sensitivity analysis. Do not re‐
solve the model. Clearly indicate
the part of the output each answer is based on.
1.
If ABC found out that they underestimated their return on invest
ment on the CRM
offering, what would be the impact of this on their estimated pr
ofit, i.e. how much
increase in the ROI from the current level of 0.4 would require
you to re‐solve the model
and change your recommendation?
2.
If the ROI for Data warehousing services went up to 0.5, how m
uch of an increase in
profit would that imply?
3.
If the VP thinks that he can increase the computer capacity by a
cquiring 10 more
computers for $72,000 (total, i.e. for all computers) annually, sh
ould he go ahead and
spend the money on these 10 computers? Why? (Note: this mone
y would not be part of
the existing operating budget)
Solve model B adding answer and sensitivity analysis reports t
o your output. Answer the
following questions based on the sensitivity analysis. Do not re‐
solve the model. Clearly indicate
the part of the output each answer is based on.
4.
If the profit requirement was reduced by 10% (from $500,000),
how much of their
spending can they decrease?
5.
If they now decided that $500,000 is low for profit, how much s
hould they increase their
spending to make 5% more profit (than $500,000)?
Submit one spreadsheet file (with 7 tabs: the model, the answer
report, and the sensitivity
report for each part, and your analysis) beginning with your firs
t initial ending with #5 as the file
name (i.e. <first initial>_<lastname>#5.xlsx, e.g. j_smith#5.xlsx
)
Model A
Decision Variables
CRM: annual amount ($) spent on CRM services
DWH: annual amount ($) spent on DWH services
DB: annual amount ($) spent on DB services
Objective Function
Maximize 0.4*CRM + 0.35*DWH + 0.4*DB
Constraints:
CRM + DWH + DB <= 1.9M (an
nual budget in $)
1.8*CRM + 1.3*DWH + 1.9*DB <= 5M (monthl
y bandwidth in MB)
3.6*CRM + 2.6*DWH + 3.8*DB <= 4320000 (
monthly M/C capacity in minutes)
CRM <= 0.4*(C
RM + DWH + DB) (diversification)
DWH <= 0.4*(
CRM + DWH + DB) (diversification)
DB <= 0.4*(
CRM + DWH + DB) (diversification)
CRM, DWH, DB >= 0 (nonn
egativity)
Model B
Decision Variables
CRM: annual amount ($) spent on CRM services
DWH: annual amount ($) spent on DWH services
DB: annual amount ($) spent on DB services
Objective Function
Minimize CRM + DWH + DB
Constraints:
0.4*CRM + 0.35*DWH + 0.4*DB >= 500,00
0 (minimum ROI)
1.8*CRM + 1.3*DWH + 1.9*DB <= 5M (m
onthly bandwidth in MB)
3.6*CRM + 2.6*DWH + 3.8*DB <= 43200
00 (monthly M/C capacity in minutes)
CRM <= 0.
4*(CRM + DWH + DB) (diversification)
DWH <= 0.4
*( CRM + DWH + DB) (diversification)
DB <= 0.
4*( CRM + DWH + DB) (diversification)
CRM, DWH, DB >= 0 (n
onnegativity)
12152011 1 Genetic Mendle’s law Patterns of .docx

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12152011 1 Genetic Mendle’s law Patterns of .docx

  • 1. 12/15/2011 1 Genetic Mendle’s law Patterns of Inheritance • Mendel’s Laws • Variations on Mendel’s Laws • The Chromosomal Basis of Inheritance • Sex Chromosomes and Sex-linked Genes 12/15/2011 2 The Field of Genetics has Ancient Roots • Hippocrates (father of medicine): particles from every part of the body travel to eggs and sperm to be passed on • Aristotle (philosopher): ‘potential’ rather than particles to produce body features
  • 2. • 19th century biologists: blending- mom and dad’s traits blend like blue and yellow paint Hippocrates Aristotle Experimental Genetics Began in an Abbey Garden • Modern genetics began in 1860s • Gregor Mendel (monk in what was then Austria- now Czech Republic) • Parents pass on discrete, heritable factors (1866) • Heritable factors retain their individuality for generations (no blending) • Studied garden peas 12/15/2011 3 • In a typical breeding experiment – Mendel mated two different, true-breeding varieties, a process called hybridization • The true-breeding parents – Are called the P generation
  • 3. • The hybrid offspring of the P generation – Are called the F1 generation – F2 generation comes next Experimental Genetics Began in an Abbey Garden • Cross: pollinating a flower of one variety with the pollen of another variety Mendel chose to work with peas: – Because they are available in many varieties – Because he could strictly control which plants mated with which – Because he could easily start his experiments with varieties that were “true-breeding” 12/15/2011 4 Some genetic vocabulary Character: a heritable feature, such as flower color
  • 4. Trait: a variant of a character, such as purple or white flowers Gene: a discrete unit of hereditary information consisting of a specific DNA (nucleotide) sequence on a chromosome Allele: alternative version of a gene Mendel’s Law of Segregation Describes the Inheritance of a Single Characteristic Performed monohybrid crosses (only 1 trait differs between the varieties) • When Mendel crossed contrasting, true-breeding white and purple flowered pea plants » All of the offspring were purple!!! Mendel discovered: A ratio of about three to one (3:1) purple to white flowers, in the F2 generation When Mendel crossed the F1 plants – Many of the plants had purple flowers, but some had white flowers
  • 5. 12/15/2011 5 Mendel’s Law of Segregation Describes the Inheritance of a Single Characteristic Mendel developed a hypothesis to explain the 3:1 inheritance pattern that he observed among the F2 offspring Four Parts: 1. First, alternative versions of genes account for variations in inherited characters which are now called alleles Allele for purple flowers Locus for flower-color gene Homologous pair of chromosomes Allele for white flowers Mendel’s Model for Inheritance Four Parts: 1. First, alternative versions of genes account for variations in
  • 6. inherited characters which are now called alleles 2. Second, for each character an organism inherits two alleles, one from each parent. These alleles may be the same or different! Locus for flower-color gene 12/15/2011 6 Mendel’s Model for Inheritance Four Parts: 1. First, alternative versions of genes account for variations in inherited characters which are now called alleles 2. Second, for each character an organism inherits two alleles, one from each parent. These alleles may be the same or different! Locus for flower-color gene 3. Third, if the two alleles at a locus differ then one, the dominant allele, determines the organism’s appearance. The other allele, the recessive allele, has no noticeable effect on the organism’s appearance
  • 7. 4. Fourth, A sperm or egg carries only one allele for each inherited trait because allele pairs separate (segregate) from each other during the production of gametes Does Mendel’s segregation model account for the 3:1 ratio he observed in the F2 generation of his numerous crosses? We can answer this question using a Punnett square 12/15/2011 7 The Punnet Square • A very convenient tool used in genetics. • Steps: – 1. Determine the parents gametes. • This may be the most important step. – 2. Match the gametes, and form possible offspring. – 3. Determine the chances of each type of offspring. A basic Punnet square:
  • 8. • Notice that the mother and father are both heterozygous. • If the dominant sperm fertilizes the dominant egg, then the offspring would be TT. – There is a 25% chance of this occurring. – 1 out of 4 will be this. 12/15/2011 8 Scientists use a “test cross” if they don’t know what the genotype of an individual is. • What is the: – Phenotype of a purple pea plant? – Phenotype of a white pea plant? – Genotype of a white pea plant? – Genotype of a purple pea plant? • How can you find out the unknown genotype of an individual?
  • 9. • You would want to breed a “known” genotype against your “unknown.” – The offspring will tell you what the “unknown” is. 12/15/2011 9 Not Just Flower Color! Vocabulary – Enough Already! • Punnett square: used to determine genotypic and phenotypic frequencies • Phenotype: an organism’s expressed traits (outward appearance) • Genotype: an organism’s genetic makeup (gene combinations) 12/15/2011 10 An organism that is homozygous for a particular gene: – Has a pair of identical alleles for that gene – Exhibits true-breeding
  • 10. An organism that is heterozygous for a particular gene: – Has a pair of alleles that are different for that gene Homologous Chromosomes Bear the Two Alleles for Each Characteristic Remember: Alleles (alternative forms) of a gene reside at the same locus on homologous chromosomes – Homozygous: both alleles match (either dominant or recessive) – Heterozygous: one allele is dominant, one is recessive 12/15/2011 11 Albinism Failure to synthesize the pigment melanin From: Introduction to Genetic Analysis, 8th Ed. Griffiths et al. The Punnet Square • A very convenient tool used in genetics.
  • 11. • Steps: – 1. Determine the parents gametes. • This may be the most important step. – 2. Match the gametes, and form possible offspring. – 3. Determine the chances of each type of offspring. 12/15/2011 12 A basic Punnet square: • Notice that the mother and father are both heterozygous. • If the dominant sperm fertilizes the dominant egg, then the offspring would be TT. – There is a 25% chance of this occurring. – 1 out of 4 will be this. Scientists use a “test cross” if they don’t know what the genotype of an individual is.
  • 12. • What is the: – Phenotype of a purple pea plant? – Phenotype of a white pea plant? – Genotype of a white pea plant? – Genotype of a purple pea plant? • How can you find out the unknown genotype of an individual? • You would want to breed a “known” genotype against your “unknown.” – The offspring will tell you what the “unknown” is. 12/15/2011 13 Independent Assortment is Revealed by Tracking Two Characteristics at Once • Dihybrid cross: cross individuals differing in two characteristics • Mendel crossed peas with round, yellow seeds (dominant traits) and peas with wrinkled, green seeds (recessive traits)
  • 13. • Determined that traits were passed independent of each other (got yellow, wrinkled offspring, for example) • Law of independent assortment: each pair of alleles segregates independently of the other pairs of alleles during gamete formation Putting Mendel’s Laws on the Chromosomes! 12/15/2011 14 Putting Mendel’s Laws on the Chromosomes! Putting Mendel’s Laws on the Chromosomes! 12/15/2011 15 Putting Mendel’s Laws on the Chromosomes! Putting Mendel’s Laws on the Chromosomes! 12/15/2011 16
  • 14. Putting Mendel’s Laws on the Chromosomes! Independent Assortment of Two Genes in the Labrador Retriever PRA = Progressive Retinal Atrophy • Coat color and ‘normal’ vision controlled by separate genes • Blanks in the figure can represent either dominate or recessive alleles • Yellow labs have coat color controlled by different gene altogether! 12/15/2011 17 In many cases, the genotype is not immediately obvious Geneticists Use The Testcross to Determine Unknown Genotypes • A testcross allows one to determine the genotype of an organism with the dominant phenotype but unknown genotype • Crosses an individual with the dominant phenotype with an individual that is homozygous recessive for a trait Offspring phenotypes tell you the unknown
  • 15. genotype Mendel’s Laws Reflect the Rules of Probability • Event certain to take place: 1; event certain NOT to take place: 0 • Probabilities of all outcomes must add to 1 • Rule of multiplication: multiply probability of two independent events happening (flipping a coin twice, for example) 12/15/2011 18 Mendel’s Laws Reflect the Rules of Probability • What about genetics? • Trihybrid cross: what’s the probability of getting homozygous recessive at all 3 locations (AaBbCc x AaBbCc)? – Probability aa: ¼ – Probability bb: ¼ – Probability cc: ¼
  • 16. Probability aabbcc: ¼ x ¼ x ¼ = 1/64 12/15/2011 19 Genetics Traits in Humans Can be Tracked Through Family Pedigrees • Many traits simple Mendelian traits: – Freckles – Widow’s peak – Free earlobes • Pedigree: family tree • Square: male, circle: female female male male with trait female with trait Genetics Traits in Humans Can be Tracked Through Family Pedigrees
  • 17. Pedigree showing the inheritance of deafness in a family from Martha’s Vineyard 12/15/2011 20 Many Inherited Disorders in Humans are Controlled by a Single Gene • Recessive disorders: – Most human genetic disorders – Most common lethal disorder: cystic fibrosis (most common among Caucasians) – Rate of disorders increases with inbreeding • Dominant disorders: – Most are non-lethal (dwarfism, extra fingers and toes) – Lethal examples: Huntington’s Diesase Many Inherited Disorders in Humans are Controlled by a Single Gene • Recessive disorders: – Most human genetic disorders – Most common lethal disorder: cystic fibrosis (most common among Caucasians)
  • 18. – Rate of disorders increases with inbreeding • Dominant disorders: – Most are non-lethal (dwarfism, webbed fingers and toes, extra fingers and toes) – Lethal examples: Huntington’s Diesase 12/15/2011 21 Concept Check A man and a woman who are both carriers of the Martha’s Vineyard deafness allele have had three children who are not deaf. If the couple has a fourth child, what is the probability that the child will be deaf? 1/4 Variations on Mendel’s Laws – i.e. Complications, Complications! 1. Incomplete Dominance 2. Multiple Alleles for a single gene 3. Pleiotropy – some genes have multiple phenotypic
  • 19. characteristics 4. Polygenic Inheritance – additive effects of 2 or more genes (Non-Mendelian Genetics) 12/15/2011 22 Incomplete Dominance in Snapdragons and Carnations Or, what if Mendel had studied snapdragons?! • Complete dominance: dominant allele always expressed, recessive allele expressed in homozygous condition • Incomplete dominance: heterozygote is intermediate to dominant and recessive alleles • Classic example: snapdragons/carnations Incomplete dominance results in intermediate phenotypes + = Incomplete Dominance in Snapdragons and Carnations 12/15/2011
  • 20. 23 Michael Brown Joseph Goldstein Nobel Prize (1985) Physiology or Medicine Cholesterol uptake lead to the discovery of Receptor Mediated Endocytosis Famial Hypercholesterolemia: Genetic Disorder Death homozygotes ~ 10 to teens heterozygotes < 50 Exceptions to Mendel’s Laws - Incomplete Dominance Familial Hypercholesterolemia 12/15/2011 24 Variations on Mendel’s Laws – i.e. Complications, Complications! 1. Incomplete Dominance 2. Multiple Alleles for a single gene
  • 21. 3. Pleiotropy – some genes have multiple phenotypic characteristics 4. Polygenic Inheritance – additive effects of 2 or more genes (Non-Mendelian Genetics) Many Genes Have More Than Two Alleles in the Population • Why only two alleles? Many genes have more • Example: blood types • A and B dominant, O recessive 12/15/2011 25 Variations on Mendel’s Laws – i.e. Complications, Complications! 1. Incomplete Dominance 2. Multiple Alleles for a single gene 3. Pleiotropy – some genes have multiple phenotypic characteristics
  • 22. 4. Polygenic Inheritance – additive effects of 2 or more genes (Non-Mendelian Genetics) A Single Gene May Affect Many Phenotypic Characteristics Pleiotropy: gene influences multiple characteristics • Example: sickle-cell disease • Causes red blood cells to become misshapen (sickle shaped) in low oxygen environments • Heterozygote usually doesn’t suffer much, but has resistance to malaria (homozygous recessive is sensitive to malaria) 12/15/2011 26 Pleiotropy: gene influences multiple characteristics • Example: sickle-cell disease Variations on Mendel’s Laws – i.e. Complications, Complications! 1. Incomplete Dominance 2. Multiple Alleles for a single gene
  • 23. 3. Pleiotropy – some genes have multiple phenotypic characteristics 4. Polygenic Inheritance – additive effects of 2 or more genes (Non-Mendelian Genetics) 12/15/2011 27 Polygenic Inheritance of Skin Color Consider: • Hypothetical example (at least three genes for skin color) • Three (at least!) ‘dark’ skin alleles for each gene • A, B, C incompletely dominant to a, b, c Polygenic inheritance: Two or more genes influence a single phenotype Genes and the Environment Temperature Soil pH ‘Nature vs Nurture’ Acid Neutral/Alkaline
  • 24. http://www.tradenets.com/cats/sirulean.htm 12/15/2011 28 Genes and the Environment ‘Nature vs Nurture’ Exercise and Sun Exposure • Many human phenotypes are influenced by both genes and environment: – Risk of heart disease – Risk of cancer – Susceptibility to alcoholism and schizophrenia – In addition to genes, sun affects skin color CITM 501 Spring/Summer 2014 Homework Assignment 5 Due Month #, 2014 @5 PM via Bb Refer to the models at the end of this document to answer the fo
  • 25. llowing questions. Solve model A adding answer and sensitivity analysis reports to your output. Answer the following questions based on the sensitivity analysis. Do not re‐ solve the model. Clearly indicate the part of the output each answer is based on. 1. If ABC found out that they underestimated their return on invest ment on the CRM offering, what would be the impact of this on their estimated pr ofit, i.e. how much increase in the ROI from the current level of 0.4 would require you to re‐solve the model and change your recommendation? 2. If the ROI for Data warehousing services went up to 0.5, how m uch of an increase in profit would that imply? 3. If the VP thinks that he can increase the computer capacity by a cquiring 10 more computers for $72,000 (total, i.e. for all computers) annually, sh ould he go ahead and spend the money on these 10 computers? Why? (Note: this mone y would not be part of the existing operating budget)
  • 26. Solve model B adding answer and sensitivity analysis reports t o your output. Answer the following questions based on the sensitivity analysis. Do not re‐ solve the model. Clearly indicate the part of the output each answer is based on. 4. If the profit requirement was reduced by 10% (from $500,000), how much of their spending can they decrease? 5. If they now decided that $500,000 is low for profit, how much s hould they increase their spending to make 5% more profit (than $500,000)? Submit one spreadsheet file (with 7 tabs: the model, the answer report, and the sensitivity report for each part, and your analysis) beginning with your firs t initial ending with #5 as the file name (i.e. <first initial>_<lastname>#5.xlsx, e.g. j_smith#5.xlsx ) Model A
  • 27. Decision Variables CRM: annual amount ($) spent on CRM services DWH: annual amount ($) spent on DWH services DB: annual amount ($) spent on DB services Objective Function Maximize 0.4*CRM + 0.35*DWH + 0.4*DB Constraints: CRM + DWH + DB <= 1.9M (an nual budget in $) 1.8*CRM + 1.3*DWH + 1.9*DB <= 5M (monthl y bandwidth in MB) 3.6*CRM + 2.6*DWH + 3.8*DB <= 4320000 ( monthly M/C capacity in minutes) CRM <= 0.4*(C RM + DWH + DB) (diversification) DWH <= 0.4*( CRM + DWH + DB) (diversification) DB <= 0.4*( CRM + DWH + DB) (diversification) CRM, DWH, DB >= 0 (nonn egativity) Model B Decision Variables CRM: annual amount ($) spent on CRM services DWH: annual amount ($) spent on DWH services
  • 28. DB: annual amount ($) spent on DB services Objective Function Minimize CRM + DWH + DB Constraints: 0.4*CRM + 0.35*DWH + 0.4*DB >= 500,00 0 (minimum ROI) 1.8*CRM + 1.3*DWH + 1.9*DB <= 5M (m onthly bandwidth in MB) 3.6*CRM + 2.6*DWH + 3.8*DB <= 43200 00 (monthly M/C capacity in minutes) CRM <= 0. 4*(CRM + DWH + DB) (diversification) DWH <= 0.4 *( CRM + DWH + DB) (diversification) DB <= 0. 4*( CRM + DWH + DB) (diversification) CRM, DWH, DB >= 0 (n onnegativity)