GENETICS Mendelian

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GENETICSMendelian HumanReview
Modified with permission from Robert Goodman
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Genetics

• The study of heredity
• Gregor Mendel (1860s) discovered the fundamental
  principles of genetics by breeding garden peas

http//www.jic.bbsrc.ac.uk/germplas/pisum/zgs4f.ht
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Alleles

• Alternative forms of genes
• Units that determine heritable traits
• Dominant alleles (T - tall pea plants)
• Recessive alleles (t - dwarf pea plants)
• Homozygous dominant
• TT - tall pea plants
• Homozygous recessive
• tt - dwarf pea plants
• Heterozygous
• Tt - tall pea plants

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Phenotype

• Outward appearance
• Physical characteristics
• Examples
• Tall pea plant
• Dwarf pea plant

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Genotype

• Arrangement of genes
• that produces phenotype
• Example
• Tall pea plant
• TT tall (homozygous dominant)
• Dwarf pea plant
• tt dwarf (homozygous recessive)
• Tall pea plant
• Tt tall (heterozygous)

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Tongue rollers vs Non-tongue rollers
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Punnett Square

• A Punnett square is used to show the combinations
  of gametes and possible offspring

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Breed the P Generation

• Tall (TT) vs. dwarf (tt) pea plants

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Breed the F1 generation

• Tall (Tt) vs. Tall (Tt) pea plants

Tt
TT
Tt
tt
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Monohybrid Cross

• A breeding experiment that tracks the inheritance
  of a single trait
• Mendels Principle of Segregation
• Pairs of genes separate during gamete formation
  (meiosis)
• Fusion of gametes at fertilization re-pairs genes

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Homologous Chromosomes
This person would have brown eyes (Bb)
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Meiosis - Eye Color
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Monohybrid Cross

• Example Cross between two heterozygotes for
  brown eyes (Bb)
• BB brown eyes
• Bb brown eyes
• bb blue eyes

BB
Bb
Bb
bb
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Dihybrid Cross

• A breeding experiment that tracks the inheritance
  of two traits
• Mendels Principle of Independent Assortment
• Each pair of alleles segregates independently
  during gamete formation (metaphase I)
• Formula 2n (n of heterozygotes)

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Independent Assortment
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Independent Assortment

• Question How many gametes will be produced for
  the following allele arrangements?
• Remember 2n (n of heterozygotes)
• RrYy
• AaBbCCDd
• MmNnOoPPQQRrssTtQq

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Answer

• RrYy 2n 22 4 gametes
• RY Ry rY ry
• AaBbCCDd 2n 23 8 gametes
• ABCD ABCd AbCD AbCd
• aBCD aBCD abCD abCd
• MmNnOoPPQQRrssTtQq
• 2n 26 64 gametes

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Independent Assortment
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Dihybrid Cross

• Example cross between round and yellow
  heterozygous pea seeds
• R round
• r wrinkled
• Y yellow
• y green

RrYy x RrYy
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Dihybrid Cross
RRYY
RRYy
RrYY
RrYy
RRYy
RRyy
RrYy
Rryy
RrYY
RrYy
rrYY
rrYy
9331 phenotypic ratio
RrYy
Rryy
rrYy
rryy
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Multiple Alleles Polygenics

• Skin color is a polygenic trait, additive effects
  (essentially, incomplete dominance) of multiple
  genes on a single trait
• Multiple genes produce a continuous distribution
  in a Bell Shape curve of degrees of light to
  dark
• Early models suggested 2 or 4 major genes
• Recent work suggests many more genes working
  together in very complex, additive and
  non-additive combinations
• AaBbCcDdEeFf http//www.as.ua.edu/ant/bi
  ndon/ant570/topics/Skincolor.PDF

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Polygenic Skin Color

• Each gene has two forms
• An allele for high melanin production, or dark
  skin (A,B,C)
• An allele for low melanin production, or light
  skin (a,b,c)
• Each dark skin allele (A,B,C) in the genotype
  adds a small but equal amount of pigment to the
  skin

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Gametes ABC ABc AbC Abc aBC aBc abC abc
ABC 6AABBCC 5AABBCc 5AABbCC 4AABbCc 5AaBBCC 4AaBBCc 4AaBbCC 3AaBbCc
ABc 5AABBCc 4AABBcc 4AABbCc 3AABbcc 4AaBBCc 3AaBBcc 3AaBbCc 2AaBbcc
AbC 5AABbCC 4AABbCc 4AAbbCC 3AAbbCc 4AaBbCC 3AaBbCc 3AabbCC 2AabbCc
Abc 4AABbCc 3AABbcc 3AAbbCc 2AAbbcc 3AaBbCc 2AaBbcc 2AabbCc 1Aabbcc
aBC 5AaBBCC 4AaBBCc 4AaBbCC 3AaBbCc 4aaBBCC 3aaBBCc 3aaBbCC 2aaBbCc
aBc 4AaBBCc 3AaBBcc 3AaBbCc 2AaBbcc 3aaBBCc 2aaBBcc 2aaBbCc 1aaBbcc
abC 4AaBbCC 3AaBbCc 3AabbCC 2AabbCc 3aaBbCC 2aaBbCc 2aabbCC 1aabbCc
abc 3AaBbCc 2AaBbcc 2AabbCc 1Aabbcc 2aaBbCc 1aaBbcc 1aabbCc 0aabbcc
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Test Cross

• A mating between to determine genotype of an
  individual of unknown genotype and a homozygous
  recessive individual
• Example C__ x cc
• CC curly hair
• Cc curly hair
• cc straight hair

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Test Cross

• Possible results

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Codominance

• In Codominance, Multiple Alleles are expressed in
  heterozygous individuals
• Example Blood ABO system
• 1. type A IAIA or Iai (AA or AO)
• 2. type B IBIB or Ibi (BB or BO)
• 3. type AB IAI B (AB)
• 4. type O ii (OO)

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Codominance

• Example Homozygous male B (IBIB)
• x Heterozygous female A (IAi)

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Codominance
Example male O (ii) x female AB (IAIB)
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Codominance

• Question If a boy has a blood type O and his
  sister has blood type AB, what are the
  genotypes and phenotypes of their parents
• boy - type O (ii) X girl - type AB (IAIB)
• OO AB

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Codominance

• Answer

Parents genotypes IAi and IBi phenotypes
A and B
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Question 7

• Charlie Chaplin, a film star, was involved in a
  paternity case. The woman bringing suit had two
  children, on whose blood type was A and the other
  whose blood type was B.
• Her blood type was O, the same as Charlie s!
• The judge in the case awarded damages to the
  woman, saying that Charlie had to be the father
  of at least one of the children.

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Answer 7A

• Obviously, the judge should be sentenced to
  Biology. For Charlie to have been the father of
  both children, his blood type would have had to
  be what?
• IA IB ? Answer
• AB
• i IAi IBi
• i IAi IBi

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Incomplete Dominance

• F1 hybrids have an appearance somewhat in between
  the phenotypes of the two parental varieties
• Example snapdragons (flower)
• red flower (RR) x white flower (rr)

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Sex Determination
Sex Chromosomes
XX chromosome - female
Xy chromosome - male
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Sex Determination
X X
X y
X X
X y
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Other Sex Determination

• The Y chromosome sometimes does not dictate its
  maleness
• Absence of a second X
• XY fruit fly is male
• XXY fruit fly is female

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Environmental Sex Determination

• Sex may be determined after fertilization
• Determined by temperature during early embryonic
  development
• Turtles produce more females at a higher
  temperature
• Alligators and many lizards produce more males at
  a higher temperature

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Sex-linked Traits

• Traits (genes) located on the sex chromosomes
• Hemophiliacs (X-linked)
• Male Pattern Baldness (X-linked)
• Color-blindness (X-linked)
• Male Ear Hair (y-linked)

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Sex-linked Traits
Sex Chromosomes
fruit fly eye color
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XN XN
XN y
XN Xn
Xn y
N normal n Hemophilia
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Male Pattern Baldness
XN XN
XN y
XN Xn
Xn y
N normal n Bald
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Colorblindness
XN XN
XN y
XN Xn
Xn y
N normal n Colorblind
http//www.toledo-bend.com/colorblind/Ishihara.htm
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Y-linked Ear-Hair
X X
X y
X X
X y
y Ear Hair
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Y linked

• 3 muslim brothers in South India

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Barr Bodies

• Barr discovered the Barr Body
• An inactive X chromosome
• a darkly staining body in the nuclei of females
• Mary Lyon, identified the Barr body as an
  inactive X chromosome
• Inactivation is random, with a 50 - 50 chance of
  inactivating the maternal or paternal X
• The mammalian female is a genetic mosaic
• some cells have the XP active
• some have the XM active

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Barr Bodies

• Fur coloration of calico cats is governed by two
  alleles (black and orange - multiple alleles )
• Both attached to the same loci on a homologous
  pair of X chromosomes
• In black fur cells orange allele is inactive
• In orange fur cells black allele is inactive
• Explained in more detail at Barr Bodies and
  Gender Verification 

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XN XN
XN y
XN Xn
Xn y
N normal n Hemophilia
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Genetic Problems

• Tay-Sachs disease
• single gene, autosomal recessive, early lethal,
  no homozygotes reproduce, carriers have normal
  phenotype
• Sickle cell anemia
• single gene, autosomal recessive, condition can
  be treated, carriers may have symptoms (sickle
  cell trait)
• Cystic fibrosis
• single gene, autosomal recessive, life can be
  prolonged, carriers have normal phenotype
• Phenylketonuria (PKU)
• single gene, autosomal recessive, can be
  diagnosed at birth, diet can treat, carriers have
  normal phenotype
• Huntingtons disease
• single gene, autosomal dominant, onset late in
  life (so patients likely to reproduce prior to
  diagnosis), no carriers
• Heart disease, high blood pressure
• multiple genes, no simple pattern of inheritance,
  genes increase susceptibility

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Sickle Cell Anemia
Sickle cell anemia one mutant gene, many symptoms
Single amino acid substitution in the hemoglobin
protein
Pain, stroke, leg ulcers, bone damage, jaundice,
gallstones, lung damage, kidney damage, eye
damage, anemia, delayed growth
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Single gene traits studied using a pedigree
Why do we need to study pedigrees to understand
Mendelian inheritance in humans?
Because The human generation time is about 20
years. Humans produce relatively few offspring
compared to most other species. Well-planned
breeding experiments are impossible.
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Conventional Symbols for Human Pedigrees
Mating
Normal male
Normal female
Normal, sex irrelevant or unknown
Between relatives
Affected male
Affected female
I
Affected, sex irrelevant or unknown
II
Last born
Sibling birth order from left to right
siblings
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Pedigree Analysis
Widows peak dominant
Attached ear lobe recessive
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Autosomal Recessive Pedigree
Many people in these pedigrees were probably
carriers - heterozygotes
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Autosomal Dominant Pedigree
No carriers
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Karyotype

• A method of organizing the chromosomes of a cell
  in relation to number, size, and type.

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Karyotyping

• Chromosomes can tell us
• an unborn baby may have a genetic disorder
• a person will be male or female
• Scientist can analyze
• chromosomes in prenatal testing
• diagnose specific diseases

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Karyotyping
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Karyotyping
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Method
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Nondisjunction
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FREQUENCY OF ABNORMALITY ()
http//www.carolguze.com/text/442-4-chromosome_abn
ormalities.shtml
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Chromosomal Abnormalities

• Down Syndrome
• Turner Syndrome
• Klinefelter Syndrome
• Cri du chat Syndrome
• Williams Syndrome
• Reciprocal Translocation Philadelphia Chromosome

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Down Syndrome
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Down Syndrome

• Down Syndrome is a genetic disorder caused by
  extra genetic material
• Over 350,000 people in the USA (1 in 800 live
  births)
• Down Syndrome symptoms vary greatly from person
  to person
• Mental retardation
• Eyes that slant upward
• Heart defects
• Increased incidence of acute leukemia
• 3 copies of chromosome 21 "Trisomy 21"

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Turners Syndrome
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Turners Syndrome

• Women and girls with Turner Syndrome have only
  one X chromosome
• Example of monosomy
• 60,000 USA girls and women (1 in 2000)
• Symptoms
• Short stature and lack of ovarian development
• Webbed neck, arms that turn out slightly at the
  elbow, and a low hairline in the back of the head
  
• 75 to 80 percent of cases the father's sperm is
  missing a sex chromosome

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Klinefelter Syndrome
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Klinefelter Syndrome

• 1 in 500 to 1 in 1000 live births
• Develop as males with subtle characteristics that
  become apparent during puberty
• Often tall
• usually do not develop secondary sex
  characteristics such as facial hair, or underarm
  and pubic hair
• Trisomy with Y chromosome and 2 X chromosomes
• The extra X chromosome is from the mother's egg
  or from the father's sperm

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Cri du chat Syndrome
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Cri du chat Syndrome

• A rare syndrome (1 in 50,000 live births) caused
  by a deletion on the short arm of chromosome 5
• French for "cry of the cat," referring to the
  distinctive cry of children with this disorder
• Caused by abnormal larynx development, which
  becomes normal within a few weeks of birth
• Infants with cri du chat have low birth weight
  and may have respiratory problems
• May have a shortened lifespan, but most have a
  normal life expectancy.
• 80 percent of the cases, the chromosome carrying
  the deletion comes from the father's sperm.

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Williams Syndrome
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Williams Syndrome

• Caused by a very small chromosomal deletion on
  the long arm of chromosome 7
• Includes the elastin gene,which encodes a protein
  that gives blood vessels the stretchiness and
  strength required to withstand a lifetime of use
• Elastin protein is made only during embryo
  development and childhood, when blood vessels are
  formed
• Because of no elastin protein
• Disorders of the circulatory system known as
  vascular disorders

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Reciprocal Translocation Philadelphia Chromosome
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Reciprocal Translocation Philadelphia Chromosome

• Abnormal chromosome in karyotype
• 46 chromosomes with a translocation between
  chromosome 9 and chromosome 22 (Philadelphia
  chromosome)
• Most of chromosome 22 has been translocated onto
  the long arm of chromosome 9
• The small distal portion of the short arm of
  chromosome 9 is translocated to chromosome 22
• Translocation found only in Chronic Myelogenous
  Leukemia (CML) patients
• the cells that produce blood cells for the body
  (the hematopoietic cells) grow uncontrollably,
  leading to cancer