All About Your Animal

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GENETICS
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GENETICS

• Study of inheritance
• Transmission of traits from one generation to the
  next
• Awareness of inheritance 10,000 years ago
• Agriculture, domestication, selective breeding
• Offspring are unique, but possess characteristics
  of both parents
• A deeper understanding of inheritance is
  relatively new

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GREGOR MENDEL

• 1822 - 1884
• Father of genetics
• Augustinian monk
• Austria, now Czech Republic
• Training in
• Agriculture
• Scientific method
• Mathematics, statistical analysis
• Studied inheritance in garden peas
• Discovered the particulate nature of inheritance

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WHY USE GARDEN PEAS?

• Available in many varieties
• Easy to maintain
• Control over mating
• Short generation time
• Numerous offspring
• No major ethical issues
• Findings applicable to other organisms

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MENDELS EXPERIMENTS

• Began with true-breeding stocks
• Purple flowers ? all purple offspring
• White flowers ? all white offspring
• Etc.

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FLOWER STRUCTURE

• Most flowers are simultaneously both male and
  female
• Carpels are female structures (?)
• Produce eggs
• Stamen are male structures (?)
• Produce sperm

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FLOWER STRUCTURE

• Pollination involves the transmission of
  sperm-containing pollen to a (female) stigma
• Fertilization follows successful pollination
• Self-pollination and cross-pollination are both
  possible

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MENDELS EXPERIMENT

• Purple x white
• Both parents are true-breeding
• Stamen (?) removed from female
• Pollen transfer
• Seeds are offspring
• F1 generation produced
• First filial generation
• Monohybrids
• F1 x F1 ? F2 generation
• Monohybrid cross

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MENDELS RESULTS

• How do you think Mendel produced the F2
  generation?
• Did Mendel need a scissors and paintbrush?
• Is this sexual reproduction?

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MENDELS RESULTS
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MENDELS RESULTS
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MENDELS RESULTS

• Mendels obtained similar results for each of the
  seven traits he studied
• One phenotype disappeared in the F1 generation
• This recessive phenotype reappeared in
  approximately ¼ of the F2 individuals
• Mendels Law of Segregation explained these
  results
• Described the particulate nature of inheritance

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LAW OF SEGREGATION

• Alternative versions of genes account for
  variations in inherited characteristics
• These alternative versions of genes are termed
  alleles
• The flower color gene exists in two forms
• Purple white
• Purple color is determined by a purple allele
• White color is determined by white alleles
• We now know that genes reside upon chromosomes
• Pairs of chromosomes ? pairs of genes

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LAW OF SEGREGATION
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LAW OF SEGREGATION

• For each character, an organism inherits two
  alleles, one from each parent
• A diploid organisms inherits one copy of each
  chromosome from each parent
• Since genes reside upon chromosomes, an organisms
  would inherit one copy of each gene from each
  parent
• These alleles may be identical or non-identical

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LAW OF SEGREGATION

• If these two alleles differ, the allele that is
  visibly apparent is termed the dominant allele,
  and the allele that is masked is termed recessive
• P purple allele (dominant)
• p white allele (recessive)
• PP ? purple flowers
• Pp ? purple flowers
• pp ? white flowers

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LAW OF SEGREGATION

• The two alleles for each character segregate
  during gamete production
• Gametes (sperm egg) are produced following
  meiosis
• Meiosis separates pairs of homologous chromosomes
• Meiosis separates pairs of alleles
• Each gamete gets one allele

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GENETICS TERMINOLOGY

• Genotype
• Combination of alleles
• Phenotype
• Visible characteristics
• Homozygous
• Both alleles are identical
• Heterozygous
• Both alleles are different

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MENDELS RESULTS
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MENDELS RESULTS
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MENDELS RESULTS
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PUNNETT SQUARE

• A Punnett square is used to determine the
  genotypes of potential offspring from a given
  mating
• The genotypes of female gametes are listed across
  one axis
• The genotypes of male gametes are listed across
  the other axis

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PUNNETT SQUARE

• A Punnett square is used to determine the
  genotypes of potential offspring from a given
  mating
• Each box represents the product of a specific
  fertilization event

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UNKNOWN GENOTYPE

• The F2 generation in a white x purple monohybrid
  cross displays a 31 phenotypic ratio and a 121
  genotypic ratio
• Individuals with the dominant phenotype may be
  homozygotes or may be heterozygotes
• 1/3 of the purple-flowered plants are expected to
  be homozygous
• 2/3 of the purple-flowered plants are expected to
  be heterozygous
• Can we determine the genotype?

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TEST CROSS

• A test cross can be used to determine the
  genotype of an individual with a dominant
  phenotype
• This individual is crossed to a homozygous
  recessive individual
• Phenotypes of offspring will uncover the
  genotype of the parent

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MULTIPLE CHARACTERISTICS

• Mendels Law of Segregation was derived from
  crosses involving one characteristic at a time
• Mendel also followed two characteristics
  simultaneously
• What do you suppose happened when Mendel
  performed a dihybrid cross?

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DIHYBRID CROSS

• Yellow seeds are dominant to green seeds
• Smooth seeds are dominant to wrinkled seeds
• YYRR (yellow, smooth) x yyrr (green, wrinkled)
• The F1 generation was all YyRy (yellow, smooth)
• What would the F2 generation look like?

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DIHYBRID CROSS
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DIHYBRID CROSS

• YYRR x yyrr ? YyRr F1 generation
• YyRr x YyRr ? more complex F2 generation
• The F2 generation consisted of individuals with
  four different phenotypes
• Yellow, round
• Yellow, smooth
• Green, round
• Green, smooth

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DIHYBRID CROSS

• YyRr x YyRr
• Fill in the genotypes of the gametes and the
  offspring in this Punnett square

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DIHYBRID CROSS

• For a moment, ignore the seed texture
• What is the yellowgreen ratio?

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DIHYBRID CROSS

• For a moment, ignore the seed color
• What is the smoothwrinkled ratio?

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DIHYBRID CROSS

• Viewing only one characteristic while ignoring
  the other generates a ratio that we have seen
  before
• The more complex ratio seen in a dihybrid cross
  results from the superimposition of two simper
  ratios

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DIHYBRID CROSS

• What is the expected frequency of each of the
  following phenotypes in this dihybrid cross?
• Y_R_ (yellow, round)
• Y_rr (yellow, wrinkled)
• yyR_ (green, round)
• yyrr (green, wrinkled)

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DIHYBRID CROSS

• The ratio Mendel observed was 31510810132
• Similar results were obtained for different
  combinations of traits
• How close is this ratio to the expected ratio?
• (First, reduce the ratio to ???1 by dividing
  all numbers by the smallest)

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INDEPENDENT ASSORTMENT

• Mendels Law of Independent Assortment
• Two pairs of alleles segregate independent of
  each other during gamete formation
• The segregation of alleles for seed color has no
  effect on the segregation of alleles for seed
  shape
• Etc.

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PROBABILITY

• Mendels laws of segregation and independent
  assortment reflect the rules of probability
• So do the results of flipping coins, rolling
  dice, etc.
• What is the chance of flipping two coins and
  getting heads on each?
• one of each?

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PROBABILITY

• What is the chance that a six will be rolled on a
  single die?
• What is the chance that an even number will be
  rolled on a single die?
• What is the chance that a six will not be rolled
  on a single die?

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PROBABILITY

• What is the chance that the card on top of a
  freshly cut deck is a jack?
• What is the chance that a randomly selected card
  is a heart?
• What is the chance that a randomly selected card
  is red?
• What is the chance that a randomly selected card
  is a face card (JQK)?
• What is the chance that a randomly selected card
  is the ace of spades?

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PROBABILITY

• What is the chance of rolling 7 on two dice?
• What is the chance of rolling 6 on two dice?
• What is the chance of rolling 2 on two dice?
• (Determine the answer of these questions
  mathematically as well as by drawing a Punnett
  square)

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PROBABILITY

• What is the chance of rolling 18 on three dice?
• What is the chance of rolling 17 on three dice?
• What is the chance of rolling 16 on three dice?
• (Determine the answer of these questions
  mathematically)

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PROBABILITY

• In the trihybrid cross AaBbCc x AaBbCc, what
  fraction of the offspring would be expected to be
  homozygous dominant for all three alleles?
• homozygous for all three pairs of alleles?
• heterozygous for all three pairs of alleles?
• homozygous for at least one pair of alleles?
• (Determine the answer of these questions
  mathematically)

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BEYOND MENDEL

• Sometimes genetics isnt quite so simple
• (Yeah, right, like you think it is simple so
  far)
• Incomplete dominance
• Codominance
• Multiple alleles
• Pleiotropy
• Epistasis
• Polygenic inheritance
• Effects of environment

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INCOMPLETE DOMINANCE

• Heterozygote has an intermediate phenotype
• e.g., Flower color in snapdragons
• Red x white ? pink
• Less red pigment
• Why arent we using R r to denote these
  alleles?

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MULTIPLE ALLELES

• Though individuals possess at most two different
  alleles for a given gene, more than two alleles
  can exist within a population
• e.g., ABO blood types
• Determined by three alleles of a single gene
• IA, IB, i
• Six different combinations of these three
  alleles are possible

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CODOMINANCE

• Heterozygote has both phenotypes
• e.g., ABO blood types
• IA allele ? A antigen
• IB allele ? B antigen
• i allele ? no antigen

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CODOMINANCE

• Heterozygote has both phenotypes
• e.g., ABO blood types
• IA allele ? A antigen
• IB allele ? B antigen
• i allele ? no antigen
• IA and IB are both dominant to i
• IAIB individuals produce both the A antigen and
  the B antigen
• Codominant

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BLOOD TYPES

• Why are blood types important?
• Confer no known adaptive value
• Matching blood types during blood transfusions is
  important
• Avoid transfusion reactions

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BLOOD TYPES

• Why are blood types important?
• Your immune system can discriminate between self
  and non-self
• Blood containing foreign molecules (antigens)
  is recognized as non-self
• The immune system attack against these foreign
  cells can be fatal
• Transfusion reaction

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BLOOD TYPES

• Why are blood types important?
• Transfusion reaction
• Blood cells will be clumped together
• Small blood vessels clogged
• Hinders blood flow to tissues beyond
• Hemolysis of RBCs
• Reduced O2-carrying ability
• Released hemoglobin precipitates in kidneys
• Kidney shutdown

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BLOOD TYPES

• Why are blood types important?
• A recipient of a blood transfusion must not
  receive blood containing any foreign antigens
• A recipient of a blood transfusion may receive
  blood lacking some of their own antigens
• e.g., A cannot receive AB or B
• e.g., A can receive O

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BLOOD TYPES
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PLEIOTROPY

• One gene ? multiple phenotypes
• e.g., Sickle-cell disease
• Anemia
• Weakness
• Heart failure
• Paralysis
• Kidney failure
• etc.

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EPISTASIS

• Multiple genes ? one phenotype
• e.g., Coat color in mice
• 934 ratio observed is a modified 9331

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POLYGENIC INHERITANCE

• Multiple genes ? one phenotype varying along a
  continuum
• Quantitative characters
• e.g., Human skin color
• e.g., Human height
• This genetic skin color model assumes three
  genes, each possessing a dark allele and a
  light allele

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POLYGENIC INHERITANCE
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POLYGENIC INHERITANCE

• Over ten loci are involved in height inheritance
  in humans
• Environmental factors are also important
• e.g., Diet
• Human height displays a bell curve distribution

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ENVIRONMENTAL EFFECTS

• Phenotype is determined in part by genotype
• Phenotype is also affected by environmental
  factors
• e.g., Hydrangea flower color is dependent upon
  soil pH

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HUMAN GENETICS

• Many human traits are genetically determined
• Eye color
• Widows peak
• Ear lobes
• Blood type
• Skin color
• Various genetic disorders
• Etc.

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HUMAN GENETICS

• Peas are very convenient model organisms for
  genetic research
• Humans are much less convenient
• Could you please reproduce with that person over
  there so I can see what your babies will look
  like?
• Etc.
• How many more reasons can you list?

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HUMAN GENETICS

• Ethics precludes controlled mating in humans
• Information is gathered through family history
• Pedigrees
• Genotypes can be inferred from phenotypes of
  several family members

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HUMAN GENETICS
Nancy Wexler tracks Huntingdon's disease in a
large family
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HUMAN GENETICS

• Many genetic disorders are inherited as simple
  recessive traits
• Albinism
• Cystic fibrosis
• Phenylketonuria
• Sickle-cell anemia
• Tay-Sachs disease
• Etc.

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HUMAN GENETICS

• Some genetic traits are more common in certain
  ethnic groups
• e.g., Cystic fibrosis
• 1/2,500 European Americans
• e.g., Sickle-cell disease
• 1/400 African Americans
• e.g., Tay-Sachs disease
• 1/3,600 Ashkenazik Jews
• Why?
• Consanguinity
• Potential benefit of mutant allele

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SICKLE-CELL ANEMIA

• Genetically determined
• Aberrant b-globin allele (HbS)
• Glutamic acid (HbA) ? valine (HbS)
• Cells sickle under low oxygen conditions
• Multiple deleterious effects

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SICKLE-CELL ANEMIA
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MALARIA

• Malaria has been and still is prevalent in
  portions of Africa, Asia, and the Middle East
• Malaria has infected 100 million people
• 1 million die yearly in Africa alone

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SICKLE-CELL ANEMIA

• The prevalence of sickle-cell anemia roughly
  parallels that of malaria
• Is there a connection?

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SLAVE TRADE

• Many of the African slaves transported to the
  Americas came from regions where malaria and
  sickle-cell anemia were prevalent
• As a result, 0.25 of African-Americans have
  sickle-cell anemia
• 10 are carriers of the sickle-cell allele

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SICKLE-CELL ANEMIA

• If the HbS allele is bad, why is its frequency so
  high in certain populations?
• Shouldnt natural selection weed it out?

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SICKLE-CELL ANEMIA

• Though having sickle-cell anemia is harmful,
  possession of a single HbS allele is beneficial
• Individuals possessing a single HbS allele
  possess an innate resistance to the malaria
  parasite
• Plasmodium parasite survives poorly in cells w/
  HbS
• Thus, natural selection preserves this allele in
  populations due to this beneficial effect
• How does this work?

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SSA MALARIA

• HbS/HbS individuals have sickle-cell anemia
• HbA/HbS individuals are only mildly anemic
• HbA/HbA individuals are normal
• Who gets killed by sickle-cell anemia?
• Who gets killed by malaria?

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HUMAN GENETICS

• Some genetic disorders are inherited as simple
  dominant traits
• Achondroplasia
• Huntingdons disease
• Polydactyly
• Why doesnt natural selection eliminate these
  alleles from populations?

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GENETIC TESTING

• Genetic testing offers a preventative approach to
  many genetic disorders
• The risk that a particular genetic disorder will
  occur can sometimes be assessed before it becomes
  problematic
• Three levels at which genetic testing can be
  performed
• Carrier recognition
• Fetal testing
• Newborn screening

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GENETIC TESTING

• Carrier Recognition
• For some genetic disorders, tests can distinguish
  homozygotes from heterozygotes (carriers)
• e.g., Cystic fibrosis (most common form)
• e.g., Sickle-cell disease
• e.g., Tay-Sachs disease
• How do you think carriers for sickle-cell disease
  are identified?
• If two potential parents are carriers, what is
  the likelihood that any particular child will
  inherit two recessive alleles and have the
  disease?

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GENETIC TESTING

• Fetal Testing Amniocentesis
• Useful by 14th 16th week of pregnancy
• Sometimes a bit earlier
• Amniotic fluid extracted (10 ml)
• Chemicals and fetal cells in fluid tested
• Culturing cells requires additional time

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GENETIC TESTING

• Fetal Testing Chorionic Villus Sampling
• Useful by 8th 10th week of pregnancy
• Fetal placental tissue removed
• Chorionic villus cells already dividing rapidly
• Karyotyping can be done immediately

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GENETIC TESTING

• Fetal Testing Ultrasound
• Noninvasive procedure
• Sound waves projected through abdomen produce
  image
• Can detect major anatomical abnormalities
• No known risk

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GENETIC TESTING

• Newborn Screening
• Simple tests can readily detect some genetic
  disorders at birth
• Some are routinely performed
• e.g., Screening for phenylketonuria (PKU)
• Mandatory screening for newborns

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GENETIC TESTING

• Fetal Testing Phenylketonuria (PKU)
• 1/12,000 births in Unites States
• Defective in catabolism of phenylalanine (a.a.)
• Breakdown products of phenylalanine reach toxic
  levels in blood
• Mental retardation results
• Modified (low-phe) diet avoids damaging effects
  of disorder

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• CHROMOSOMAL BASIS OF INHERITANCE

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MENDEL REDISCOVERED

• Mendels work collected dust for years
• Rediscovered in 1900
• What were these heritable factors (genes)
  described by Mendel?

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CELL DIVISION

• 1875 Mitosis understood
• 1890s Meiosis understood
• 1902 Chromosome Theory of Inheritance
• Walter Sutton and others, independently

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INHERITANCE

• Walter Sutton (1902)
• Columbia University
• Chromosome Theory of Inheritance
• Noted that chromosomes segregate in a manner
  similar to Mendels genes
• Proposed that genes reside upon chromosomes
• Genes segregate as a result of chromosomal
  segregation

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INHERITANCE

• Thomas Hunt Morgan (1909)
• Columbia University
• Initially skeptical of Suttons Chromosome
  Theory of Inheritance
• Ultimately established that genes reside upon
  chromosomes
• Received Nobel Prize in 1933

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INHERITANCE

• Thomas Hunt Morgan (1909)
• Lord of the Flies
• Used fruit flies
• Drosophila melanogaster

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DROSOPHILA

• Drosophila melanogaster
• Common fruit fly
• Very amenable to genetic analysis
• What are some of the features that make this so?

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DROSOPHILA

• Morgan continually searched for fruit flies with
  variant phenotypes
• Mutants
• Ultimately discovered a white-eyed male
• Red-eyed is wild-type

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MORGANS CROSSES

• White ? x red ? ? F1 red ? ?

?
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MORGANS CROSSES

• F1 red ? x F1 red ? ? F2 red ?, red white ?

?
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SEX LINKAGE

• Sex determination in fruit flies involves X and Y
  chromosomes
• XX female
• XY male
• Inheritance of eye color correlated to the
  inheritance of the sex chromosomes
• This gene resided upon the X chromosome
• Genes do reside on chromosomes!!!

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SEX DETERMINATION

• Sex determination differs between species
• Sometimes involves sex chromosomes
• e.g., humans, Drosophila, etc.
• Sometimes does not involve sex chromosomes
• e.g., Honeybees, many reptiles, etc.

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SEX LINKAGE

• In both humans and Drosophila, the X chromosome
  contains numerous genes, while the Y chromosome
  possesses very few
• Genes on the X chromosome are termed sex-linked
• Display unique patterns of inheritance

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SEX LINKAGE

• Many human genetic disorders are sex-linked
• Color blindness
• Duchenne muscular dystrophy
• Hemophilia
• Recessive sex-linked disorders are more common in
  males than in females
• Can you explain why?

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SEX LINKAGE

• Male hemophiliac x non-hemophiliac female
• Female is either a homozygote or a carrier
• Could a male be a carrier for a sex-linked
  disorder?

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SEX LINKAGE

• Non-hemophiliac male x female carrier
• Hemophilia Its always moms fault

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GENOME MUTATIONS

• Change in chromosome number
• Can happen aberrantly during cell division
• e.g., Down syndrome (trisomy 21)
• Why do we never see trisomy 1 or trisomy 6, etc.?

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GENOME MUTATIONS

• Alterations in chromosome number can be very
  problematic or even fatal
• Half of the human population possesses an extra
  copy of the X chromosome
• How are negative effects avoided?

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GENOME MUTATIONS

• Human females possess an extra copy of the X
  chromosome
• Negative effects are absent
• Only one X chromosome is active in each cell
• X inactivation ? Barr bodies