Download Heredity

Heredity
Genetics
• The study of the mechanism of
heredity
• Genetics will play a critical role in medicine
in the future due to the Human Genome
Project
– We now have the sequence of human DNA
– The next step will be to look at that DNA and
understand the genes within
– Already, genetic testing may be influencing
your life (beyond if you commit a crime )
What is genetics?
• The term "genetics" is
derived from the word
“gene".
• Recall that…
– All DNA is grouped into 46
chromosomes (23 pairs)
– A chromosome is a collection of
genes
– A gene is a collection of triplets
– A triplet is a DNA code for a particular amino acid
– A chain of amino acids forms a polypeptide
• So, essentially genes tell our cells which
proteins to make.
Genes
• The protein coded for by a
gene may create a particular
heritable trait.
– i.e. blood type, hair color, eye
color etc.
• The protein may make an ion
channel, an enzyme, a
structure, etc.
Mutated Genes = Mutated Proteins
•
•
•
•
•
Muscular Dystrophy
Cystic Fibrosis
Achondroplasia
PKU
Black Plague/AIDS
Normal
MD
There are many ways to mutate a
protein
Genes
Fair Skin???
Green Eyes???
Alleles
Alleles: You have
two copies of each
gene. Each copy is
called an allele.
Alleles Represent Separate Genes
• In the case of eye color, you may have an
allele to make pigment (brown here) or
you may lack pigment (blue eyes).
Blue eyes
allele
Brown eyes
allele
Alleles
• Matched genes at the same locus on
homologous chromosomes
• Homozygous – two alleles controlling a
single trait are the same
– Alleles are given letter names, for example
the allele for eye color is B.
– Someone homozygous brown eyed is BB
• Heterozygous – the two alleles for a trait
are different
– Someone heterozygous is Bb (where the
little b designates a gene that codes for
another color.
Alleles
• Dominant – an allele masks
or suppresses the expression
of its partner
– Designated by capital letters
• Recessive – the allele that is
masked or suppressed
– Recessive traits are only expressed
if both alleles carry the recessive
gene.
– Designated by lower-case letter.
Brown is
dominant so
the person
will have
brown eyes
Eye Color
http://www.ideum.com/genetics-eyecalculator.html
Genotype and Phenotype
• Genotype – the genetic makeup
• Phenotype – the way one’s genotype is
expressed
The phenotype is
brown eyes
The genotype could
BB
or
Bb
• Transition
Randomizing the Gene Pool
•
At this point we understand alleles, so next we
will go into how these alleles are mixed up as
they are passed on to offspring.
• Three things randomize how alleles make it
into offspring.
1. Independent assortment during meiosis
2. Crossing over prior to meiosis
3. Random fertilization (only one egg/sperm
wins)
Why Randomize?
• The American Elm is subject to Dutch Elm
Disease. The Siberian is less susceptible.
• HIV/Black Plague
– 10% of Europeans are
resistant to AIDS because
they have a genetic mutation
that also provided resistance
to Bubonic plague.
• The Cheetah
1. Independent
Assortment
During Meiosis
• Chromosomes
are randomly
distributed to
daughter cells
• Members of the
allele pair for
each trait are
segregated
during meiosis
1. Independent
Assortment
During Meiosis
• Chromosomes
are randomly
distributed to
daughter cells
• Members of the
allele pair for
each trait are
segregated
during meiosis
1. Independent assortment
during meiosis (cont.)
• The number of different types of gametes can be
calculated by this formula:
2n, where n is the number of homologous pairs
• In a man’s testes, the number of gamete types
that can be produced based on independent
assortment is 223, which equals 8.5 million
possibilities
• If you had 23 bags, each with a pair of
chromosomes, and went down the line selecting
one chromosome of the pair, there are 8.5
million different combinations.
2. Crossing over prior to meiosis
• Early in meiosis, chromosomes will
actually swap genes.
2. Crossing over prior to meiosis
• If two genes are far apart, they are distributed
randomly. Some genes are not far apart, say
hair color and skin fairness, so redheads usually
have fair skin.
Why cross over?
3. Random fertilization (only one
egg/sperm wins)
• A single egg is fertilized by a single sperm
in a random manner
• Considering independent assortment and
random fertilization, an offspring
represents one out of 72 trillion (8.5 million
 8.5 million) zygote possibilities
• transition
Genetics
• How then do we figure
out what are the likely
mixes of alleles we can have.
• The best tool is the Punnet square.
Modes of Inheritance
•
There are three main types of inheritances
1. Autosomal Dominant
2. Autosomal Recessive
3. X- linked (sex-linked)
•
•
•
X- linked indicates a gene on the X
chromosome. Sex linked genetics are different
because there are not a pair of identical
chromosomes.
Autosomal indicates a gene on any
chromosome other than X.
The next few slides show the basics.
Dominant
If the dominant gene
is possessed, the
phenotype is seen.
Recessive
Recessive genes
must be
homozygous to
show the phenotype
X-linked
In males, the mutation is
seen.
In females, the mutation
is subject to
dominance/recessive
Dominant-Recessive
Inheritance
• Examples of dominant disorders:
achondroplasia (type of dwarfism) and
Huntington’s disease
• Examples of recessive conditions:
albinism, cystic fibrosis, and Tay-Sachs
disease
• Carriers – heterozygotes who do not
express a trait but can pass it on to their
offspring
Incomplete Dominance
• Heterozygous individuals have a phenotype intermediate
between homozygous dominant and homozygous
recessive
• Sickling gene is a human example when aberrant
hemoglobin (Hb) is made from the recessive allele (s)
SS
=
normal Hb is made
Ss
=
sickle-cell trait (both aberrant and
normal Hb is made)
ss
=
sickle-cell anemia (only aberrant
Hb is made)
Multiple-Allele
Inheritance
A
• Genes that exhibit more than
two alternate alleles
• ABO blood grouping is an
example
• Three alleles (IA, IB, i)
determine the ABO blood type
in humans
• IA and IB are codominant (both
are expressed if present), and i
is recessive
B
A
ABO Blood Groups
A
Blood Allele
Distributions:
Just for
Interest
B
O
Blood Allele Distributions:
Just for Interest: A Type
Blood Allele Distributions:
Just for Interest: B Type
Blood Allele Distributions:
Just for Interest: O Type
Polygene Inheritance
• Depends on several different gene pairs at
different loci acting in tandem
• Results in continuous phenotypic variation
between two extremes
• Examples: skin color, eye color, and
height
Polygenic
Inheritance of
Skin Color
We still don’t know it all.
• Just when people thought they had it down,
along came chromosome 15 deletions.
– Prader-Willi syndrome if mutations is
inherited from the father
• obesity, mental retardation, short stature. (abbreviated PWS)
– Angelman syndrome if mutation is inherited
from the mother
• uncontrollable laughter, jerky movements, and other motor
and mental symptoms. (abbreviated AS)
• During gametogenesis, certain genes are
methylated and tagged as either maternal or
paternal
• Developing embryos “read” these tags and
express one version or the other
PWS
AS
PWS
Mouse
model
AS
Mouse
model
We still don’t know it all.
Extrachromosomal
(Mitochondrial) Inheritance
• Some genes are in the mitochondria
• All mitochondrial genes are transmitted by
the mother
• Unusual muscle disorders and
neurological problems have been linked to
these genes
Genetic Screening, Counseling,
and Therapy
• Newborn infants are screened for a
number of genetic disorders: congenital
hip dysplasia, imperforate anus, and PKU
• Genetic screening alerts new parents that
treatment may be necessary for the wellbeing of their infant
• Example: a woman pregnant for the first
time at age 35 may want to know if her
baby has trisomy-21 (Down syndrome)
Carrier Recognition
• Identification of the heterozygote state for a
given trait
• Two major avenues are used to identify carriers:
pedigrees and blood tests
• Pedigrees trace a particular genetic trait through
several generations; helps to predict the future
• Blood tests and DNA probes can detect the
presence of unexpressed recessive genes
• Sickling, Tay-Sachs, and cystic fibrosis genes
can be identified by such tests
Pedigree
Analysis
Fetal Testing
• Is used when there is a known risk of a
genetic disorder
• Amniocentesis – amniotic fluid is
withdrawn after the 14th week and
sloughed fetal cells are examined for
genetic abnormalities
• Chorionic villi sampling (CVS) – chorionic
villi are sampled and karyotyped for
genetic abnormalities
Fetal Testing
Genetic Testing Now
• Chromosome Studies
– Pedigree and karyotyping
• DNA Studies (indirect and direct)
– Sequence the gene or a part of the gene
• Protein Truncation studies
– See if the protein is too small
• Biochemical testing
– Test to see if there is a physiological
impairment.
Human Gene Therapy
• Genetic engineering has the potential to
replace a defective gene
• Defective cells can be infected with a
genetically engineered virus containing a
functional gene
• The patient’s cells can be directly injected
with “corrected” DNA
Mutation
• Change in a gene or chromosome
• Causes an abnormal trait
Mutagen
• Agent that causes mutations
– Cigarette smoke
– Pesticides
– X-rays
– Ultraviolet light
– Nuclear radiation
Mutations
•
If there is an error in the DNA, that error
may be seen as a mutation. There are
three main types of mutation.
1. Loss of function
1. Tay-Sachs, PKU, Niemin-Pick's
2. Partial loss of function
1. Cystic fibrosis and sickle-cell anemia
3. Gain of function (and that may not be
good)
1. Make too much of something as in
epilepsy
Aneuploidy
• Mutations involve changes in single
genes.
• Aneuploidy is when
extra-chromosomes
exist in the genome
because of errors
during meiosis.
Trisomy 21
Down Syndrome
Maternal Age & Down
Syndrome
Down Syndrome
•
•
•
•
Large tongue
Flat face
Slanted eyes
Single crease across
palm
• Mental retardation
– Some are not
Trisomy 18
Edward Syndrome
Edward Syndrome
•
•
•
•
•
•
•
Heart defects
Displaced liver
Low-set ears
Abnormal hands
Severe retardation
98% abort
Lifespan < 1 year
Trisomy 13
Patau Syndrome
Patau Syndrome
• Cleft lip and palate
• Extra fingers & toes
– polydactylism
• Defects
– Heart
– Brain
– Kidneys
• Most abort
• Live span < 1 month
Klinefelter Syndrome
Klinefelter Syndrome
•
•
•
•
Breast development
Small testes
Sterile
Low intelligence
– Not retarded
Turner Syndrome
Turner Syndrome
• Short
• Not go through
puberty
• Produce little
estrogen
• Sterile
• Extra skin on neck
Crosses
• Be able to cross any combination of
homozygotes and heterozygotes with
dominant, recessive, and sex-linked
mutations.
Crosses to Know
If the mutation is dominant
Know: What the
genotypes are and
their ratios, what
the phenotypes are
and their ratios
BB
Bb
BB
BB x BB
BB x Bb
BB x bb
Bb
BB x Bb
Bb x Bb
bb x Bb
bb
BB x bb
Bb x bb
bb x bb
bb
Crosses to Know
If the mutation is dominant
Know: What the
genotypes are and
their ratios, what
the phenotypes are
and their ratios
Crosses to Know: Just
a Start
If the mutation is dominant
4 BB
4 Brown
BB
Bb
BB
Bb
bb
B B
B BB BB
B BB BB
B b
B BB Bb
b
bb
Know: What the
genotypes are and
their ratios, what
the phenotypes are
and their ratios
Bb bb
1 BB: 2 Bb : 1 bb
4 3 brown: 1 blue
Crosses to Know: Just
a Start
If the mutation is dominant
Know: What the
genotypes are and
their ratios, what
the phenotypes are
and their ratios
Crosses to Know
If the mutation is recessive
Know: What the
genotypes are and
their ratios, what
the phenotypes are
and their ratios
BB
Bb
BB
BB x BB
BB x Bb
BB x bb
Bb
BB x Bb
Bb x Bb
bb x Bb
bb
BB x bb
Bb x bb
bb x bb
bb
Crosses to Know
If the mutation is recessive
Know: What the
genotypes are and
their ratios, what
the phenotypes are
and their ratios
Crosses to Know
If the mutation is recessive
Know: What the
genotypes are and
their ratios, what
the phenotypes are
and their ratios
Crosses to Know
Sex – linked Crosses
Know: What the
genotypes are and
their ratios, what
the phenotypes are
and their ratios
XX
XhX
XhXh
XY
XX x XY
XhX x XY
XhXh x XY
XhY
XX x XhY
XhX x XhY
XhXh x XhY
Crosses to Know
Sex – linked Crosses
Know: What the
genotypes are and
their ratios, what
the phenotypes are
and their ratios
Crosses to Know
Sex – linked Crosses
Know: What the
genotypes are and
their ratios, what
the phenotypes are
and their ratios
A man & woman are both carriers
(heterozygous) for albinism.
What is the chance their children
will inherit albinism?
AA = Normal
pigmentation
Aa = Normal
pigmentation
(carrier)
Man = Aa
Woman = Aa
aa = Albino
A
A
a
a
A
a
A
AA
Aa
a
Aa
aa
AA
Aa
Genotypes
1 AA, 2Aa, 1aa
Phenotypes
Aa
aa
3 Normal
1 Albino
Probability
25% for albinism
A man & woman are both carriers
(heterozygous) for PKU disease.
What is the chance their children
will inherit PKU disease?
PP = Normal
Pp = Normal
(carrier)
P
p
P
PP
Pp
p
Pp
pp
pp = PKU
disease
PP
Pp
Genotypes
1 PP, 2Pp, 1pp
Phenotypes
Pp
pp
3 Normal (2 carriers)
1 PKU disease
Probability
25% for PKU disease
A man with sickle cell anemia
marries a woman who is a
carrier. What is the chance their
children will inherit sickle cell
anemia?
SS = Normal
Ss = Normal
(carrier)
S
s
s
Ss
ss
s
Ss
ss
ss = Sickle Cell
Ss
ss
Genotypes
2 Ss, 2ss
Phenotypes
Ss
ss
2 Normal (carriers)
2 Sickle cell
Probability
50% for Sickle cell
A man with heterozygous
dwarfism marries a woman who
has normal height. What is the
chance their children will inherit
dwarfism? Dwarfism is dominant.
DD = Dwarf
Dd = Dwarf
dd = Normal
d
d
D
Dd
Dd
d
dd
dd
Dd
Dd
Genotypes
2 Dd, 2dd
Phenotypes
dd
dd
2 Normal
2 Dwarfs
Probability
50% for Dwarfism
X-linked Recessive Traits
• Alleles are on the X chromosome
• Inheritance pattern different in males and
females
XH XH = Normal Female
XH Xh = Normal Female
(Carrier)
Xh Xh = Hemophilic
Female
XHy =
Normal Male
Xhy =
Hemophiliac Male
A man with hemophilia marries a
normal woman who is not a
carrier. What is the chance their
children will inherit hemophilia?
Hemophilia is X-linked recessive.
Xh XH = Normal Female
XH Xh = Normal Female
(Carrier)
Xh Xh = Hemophilic
Female
XH
XH
Xh
XH Xh
XH Xh
y
XHy
XHy
XHy =
Normal Male
Xhy =
Hemophiliac Male
XH
XH
Genotypes
Xh
XH
Xh
XH
Xh
2 XH
Xh, 2XHy
Phenotypes
y
XHy
2 Carrier Females
XHy
2 Normal Males
Probability
O% for Hemophilia
A normal man marries a normal
woman who is a carrier for
hemophilia. What is the chance
their children will inherit
hemophilia?
The most common type of
hemophilia is linked to a
mutation that occurred in
Queen Victoria
Xh XH = Normal Female
XH Xh = Normal Female
(Carrier)
Xh Xh = Hemophilic
Female
XH
Xh
XH
XH XH
XH Xh
y
XHy
Xhy
XHy =
Normal Male
Xhy =
Hemophiliac Male
XH
Xh
Genotypes
XH
XH
XH
XH
Xh
XH XH , XH Xh, XHy,
Xhy
Phenotypes
y
XHy
Xhy
2 Normal Females
(1 carrier)
1 Normal Males
1 Male Hemophiliac
Probability
50% for Male Hemophilic
0% for Female Hemophilic
j