Download • Recognize Mendel`s contribution to the field of genetics. • Review

Human Genetics (Learning Objectives)
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Recognize Mendel’s contribution to the field of genetics.
Review what you know about a karyotype: autosomes and sex chromosomes.
Understand and define the terms: characteristic, trait, true-breeder, genotype,
phenotype, allele, autosomal dominant and recessive traits, and a monohybrid
cross.
What is a test cross and when is used?
Learn how to use the Punnett square to determine:
– genotypes and phenotypes and probability of offspring for autosomal
dominant or recessive traits.
– the probability of passing of an X-linked gene and the phenotype to girls or
boys based on the genotypes of the parents.
Define X-linked genes and explain how the location of a gene on the X
chromosome affect its gender-related transmission and pattern of inheritance.
Review the factors affecting the phenotypes of Mendelian characters and provide
examples for each: incomplete dominance, co-dominance & multiple allele,
pleiotropy, polygenic inheritance, environmental effect, and epigenetics.
Explain how gender is determined in mammals.
Explain X-inactivation and why is it present only in cells of females only and
genetic imprinting.
Explain the pattern of inheritance of genes present on the mitochondrial DNA.
Genetics (Plan)
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Field of Heredity and Patterns of inheritance
Karyotype and terminology
Mendel, his contributions, and system he used
Mendelian pattern of inheritance of a single character and
applications (Student work sheets Q1 & Q2)
Mendelian Pattern of inheritance of 2 characters at the same
time
The laws of probability
Sex determination and pattern of inheritance of sex-linked
genes (Student work sheets Q1 & Q2)
X-inactivation
Factors influencing the phenotype of Mendelian characters
Patterns of Inheritance
Gregor Mendel
- Studied variation in plants, patterns of
inheritance in garden peas
- Used math to explain biological phenomena
The chromosome pairs 1 trough 22
are autosome
These are sex chromosomes
Terminology
Character or characteristic: a heritable
feature e.g. flower color
Trait: variant of the character e.g. purple or
white
Mendel focused on characters with two
variant phenotypes “either-or” traits
Mendel had control over
which plants he crossed
Colored Cotton Campbell video
http://www.dnaftb.org/
dnaftb/1/concept/
Mendel started with
True-breeding plants
F1 generation
F2 generation
F2 ratio
Purple flower- dominant trait
White flower- recessive trait
Mendel worked with pea
plant characteristics with
two traits each
Mendel was looking for a model that can
account for the 3:1 ratio that he observed
in the F2 generation
Mendel’s Model
1. An organism inherits two alleles (one
from each parent).
2. One allele is dominant and the other is
recessive
3. The two alleles segregate (separate)
during gamete formation (Mendel’s law
of segregation)
A Punnett
square
predicts the
results
of a genetic
cross
between
individuals
of known
genotype.
Vocabulary used in Genetics
An organism with two identical alleles is
homozygous for that character.
Organisms with two different alleles for a character
is heterozygous for that character.
A description of an organism’s traits is its
phenotype.
A description of its genetic makeup is its
genotype.
Test Cross
Used to determine
the genotype of a
dominant trait
Pedigree Analysis
Mendelian characters of humans
• A pedigree can help us understand the
past and to predict the future.
• We can use the normal Mendelian rules,
to predict the probability of specific
phenotypes.
1. Pedigree analysis reveals Mendelian
patterns in human inheritance
2. Many human disorders follow Mendelian
patterns of inheritance
Examples of Genetic Disorders
http://www.ygyh.org/
Tay-Sachs
Sickle Cell Disease
Cystic Fibrosis
Huntington Disease
Segregation of characters
• Monohybrid cross- inheritance of one
character
• Dihybrid cross- inheritance of 2 characters
Crossing true-breeding plant that have
yellow, round seeds (YYRR) with truebreeding plants that have green, wrinkled
seeds (yyrr).
If the two pairs of
alleles segregate
independently of each
other
Gametes:
P generation YR and yr
F1 generation YR, Yr,
yR, and yr
These combinations
produce four distinct
phenotypes in a
9:3:3:1 ratio.
Probability Rules Applied to Monohybrid
Crosses
The multiplication rule:
The probability that two or more independent
events will occur together is the product of
their individual probabilities
The rule of addition:
The probability that any one of two or more
exclusive events will occur is calculated by
adding together their individual probabilities
Mendelian inheritance reflects rule
of probability
What is the probability of obtaining a
homozygote dominant?
The probability of each independent allele is
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The probability of two independent alleles occurring
together
Homozygote dominant
X
=
Homozygote recessive
X
=
What is the probability of obtaining a
heterozygote?
Under the rule of addition, the probability of
an event that can occur two or more
different ways is the sum of the separate
probabilities of those ways.
Heterozygote
+
=
X and Y Chromosomes
X chromosome
- Contains > 1,500 genes
- Larger than the Y chromosome
- Acts as a homolog to Y in males
Y chromosome
- Contains 231 genes
- Many repeated DNA segments
Figure 6.2
Anatomy of the Y Chromosome
Pseudoautosomal regions
(PAR1 and PAR2)
- 5% of the chromosome
- Contains genes shared with X
chromosome
Male specific region (MSY)
- 95% of the chromosome
- Contains majority of genes
including SRY and AZF (needed for
sperm production)
Figure 6.3
SRY Gene
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Encodes a transcription factor protein
Controls the expression of other genes
Stimulates male development
Developing testes secrete anti-Mullerian
hormone and destroy female structures
• Testosterone and dihydrotesterone (DHT)
hormones are secreted and stimulate male
structures
Sex determination in Mammals:
the X-Y system
Karyotype designation: 46, XY (male)
46, XX (female)
Germ cells in testes (XY) produce sperms with
X: 50%
Y: 50%
Germ cells in ovaries (XX) produce only
X eggs
• The sex chromosomes have genes for many
characters unrelated to sex
• Each conception has about a fifty-fifty chance of
producing a particular sex
Y and X chromosomes are only partially
homologous, they pair together during meiosis but
rarely undergo crossing over
Synapsis of the X and Y
chromosomes during
prophase of meiosis I
http://www.hhmi.org/news/popups/
page_ani.html
Femaleness in mammals is
the "default" program.
SRY gene (for sexdetermining region Y)
- located on the short (p)
arm
- the master switch that
triggers the events that
converts the embryo into a
male
http://users.rcn.com/jkimball.ma.ultranet/BiologyPa
ges/S/SexChromosomes.html
Evidence
• Humans born with XXY, XXXY, and even XXXXY
abnormality, despite their extra X chromosomes, are
males.
• XX humans have a translocation placing SRY on the
X chromosome (male phenotype with testicular
tissue)
• XY humans with a defective SRY are female
• Transgenic female mice (XX) with an SRY gene are
phenotypically males with testis
The inheritance of genes of X chromosome
follows special rules, because:
• males have only a single X chromosome
• almost all the genes on the X have no
counterpart on the Y
• any gene on the X, even if recessive in
females, will be expressed in males.
• Genes are described as sex-linked or Xlinked.
X-linked Diseases
Hemophilia A, a blood clotting disorder caused by
a mutant gene encoding the clotting factor VIII
Duchenne muscular dystrophy
http://www.ygyh.org
Color blindness (X-linkage)
http://www.biology.arizona.edu/human_bio/proble
m_sets/color_blindness/color_blindness.html
Human Chromosomes
Homologous autosomes: 22 pairs = 44 chromosomes
Sex chromosomes one pair XX or XY
(X and Y share partial homology)
Dose of expressed genes?
X-inactivation
In females, only one of the X chromosomes is active.
The second is inactivated
The inactive X chromosome appears as a condensed
chromosome during interphase (Barr body)
http://users.rcn.com/jkimball.ma.ultranet/BiologyPage
s/S/SexChromosomes.html
Hemophilia A
X
Y
X
XX
XY
Xh
XhX
XhY
In XhX heterozygote female, which X is active?
X-inactivation is random: 50% of cells Xh
50% of cells X
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/SexChromosomes.html
X Inactivation
A female that expresses the phenotype
corresponding to an X-linked gene is a
manifesting heterozygote (calico cats)
Figure 6.12
The orange and black pattern on tortoiseshell
cats is due to patches of cells expressing an
orange allele while others expressing the nonorange allele.
Y-linked genes
The Y chromosome in males has 70 to 200 gene
genes whose protein products are involved in:
a. control of changing sex of the fetus from female to
male
b. development of male testes
c. male fertility
http://ghr.nlm.nih.gov/chromosome=Y
During fertilization sperm brings only the
nuclear DNA, all mitochondrial DNA is
maternal from the egg.
No Mendelian patterns of inheritance
Can be used to determine maternal lineage
Chromosomal abnormalities caused by non-disjunction of
• Homologous chromosomes during Meiosis I
• Sister chromatids during Meiosis II
Factors Affecting Phenotypic Expression
of Mendelian inherited characteristics
1.
2.
3.
4.
5.
6.
7.
Incomplete dominance
Multiple alleles- co-dominance
Pleiotropy
Polygenic inheritance
Epistasis
Environmental effect
Epigenetic factors
1. Incomplete dominance
Genotypic ratio same
as phenotypic ratio
Incomplete dominance affects severity of disease
Genotypes:
HH
Homozygous
for ability to make
LDL receptors
Hh
Heterozygous
hh
Homozygous
for inability to make
LDL receptors
LDL
LDL
receptor
Cell
Phenotypes:
Normal
Mild disease
Severe disease
2. Multiple alleles, the human ABO blood system
ABO Blood grouping test
Multiple alleles of the ABO blood system
- Three alleles, IA, IB, and I.
Both the IA and IB alleles are dominant to the i
allele
The IA and IB alleles are co-dominant to each
other.
- Because each individual carries two alleles,
there are six possible genotypes and four
possible blood types.
3. Pleiotropy
- A single gene may affect many phenotypic
characteristics involving multiple systems
- Sickle cell Disease http://www.ygyh.org/
Individual homozygous
for sickle-cell allele
Sickle-cell (abnormal) hemoglobin
Abnormal hemoglobin crystallizes,
causing red blood cells to become sickle-shaped
Sickle cells
Clumping of cells
and clogging of
small blood vessels
Breakdown of
red blood cells
Physical
weakness
Impaired
mental
function
Anemia
Heart
failure
Paralysis
Pain and
fever
Pneumonia
and other
infections
Accumulation of
sickled cells in spleen
Brain
Spleen
Damage to
damage other organs damage
Rheumatism
Kidney
failure
4. Polygenic inheritance
Quantitative
characters show
additive effect of
multiple genes, e.g
skin color and
height in humans
5. Epistasis
Phenotype is
determined by two
separate genes, e.g
coat color in mice
B coat color gene
C modifier gene
6. Environmental effects
Phenotype of Hydrangea flower color
• Blue flowers in highly acid soil
• Pink flowers in neutral or slightly acid soil
7. Epigenetic factors
Gene expression is impacted by chemical
modification of chromatin
• DNA methylation
• histone deacetylation
Prenatal Testing and Genetic Counseling
Technological tools
• Sampling of fetal cells
a. Amniocentesis
b. Chorionic Villus Sampling
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Biochemical tests
DNA testing- karyotyping and others
Chorionic Villus Sampling
(CVS)
Genetic Testing & Personalized
Medicine
(Learning Objectives)
1. Recognize the presence of common mutation within members
of the human population (polymorphisms)
2. Recognize that information about such polymorphisms can be
used for several purposes, such as:
– Mutational analysis of disease causing genes
– Genome –wide scanning for disease predisposition genes
– Personalized Medicine
Single Nucleotide Polymorphism
(SNP)
Variations in the DNA sequences of humans
affect :
- Disease development
- Response to: toxins, drugs, vaccines,
and chemotherapy.
Genome-wide screening
• Genetic variation in human population
• Correlation of certain base variability with
proximity to a disease causing gene
• SNPs- single nucleotide polymorphisms
http://topics.nytimes.com/top/news/national/series/dnaage/i
ndex.html
http://www.pathway.com/
Pros & Cons
Genetic Information Nondiscrimination Act
GINA Bill