Transcript 3. Fundamentals of human genetics.methods of research of human

Fundamentals of human
genetics. Human hereditary
diseases. Methods of
research of human heredity
Ass. Nedoshytko Khrystyna
Genetic Terminology
Genotype- the alleles
a person has
Phenotype- the
observable trait a
person has
Dominant- Alleles
affect masks the other
allele it is paired with
Recessive- Alleles
affect is masked by
the other allele it is
paired with.
Homozygous- Pair of
alleles for a trait are
identical
Heterozygous- Pair of
alleles for a trait are not
identical
Hybrid- Inherit nonidentical alleles for a trait
VISUAL
REPRESENTATION
A pair of homologous chromosomes,
each in the unduplicated state (most
often, one from a male parent and its
partner from a female parent)
Heterozygous
Pair of Chromosomes
Gene
Locus (loci)
Alleles
Heterozygous
Homozygous
Homozygous
A gene locus (plural, loci), the
location for a specific gene on
a specific type of chromosome
A pair of alleles (each being a
certain molecular form of a gene)
at corresponding loci on a pair of
homologous chromosomes
Three pairs of genes (at three
loci on this pair of homologous
chromosomes); same thing as
three pairs of alleles
Homologous Chromosomes
Homologous autosomes are
identical in length, size, shape,
and gene sequence
Sex chromosomes are
nonidentical but still homologous
Homologous chromosomes
interact, then segregate from one
another during meiosis
DNA
DNA and proteins
Nucleosome
arranged as cylindrical fiber
Histone
Human Karyotype
1
13
2
3
4
14
15
16
5
17
6
18
7
8
9
19
20
21
10
22
11
12
XX
(or XY)
Karyotype Preparation
Cultured cells for 3 to 4 days in the presence of
phytohaemagglutinin (mitogen) and
arrested at metaphase
– This is when cells are most condensed and
easiest to identify Arrested cells are broken
open
Metaphase chromosomes are fixed and
stained (how many copies of each chromosome
in one cell?)
Chromosomes are photographed through
microscope
Photograph of chromosomes is cut up and
arranged to form a karyotype diagram
Cotton Rat
(Sigmodon hipsidus)
Karyotypes
•The Alaskan king crab has
208 chromosomes.
•The fruit fly has 4.
•Number has nothing to do
with complexity of the
organism
Pied Kingfisher (Ceryle rudis)
Carrion Beetle
(Phosphuga atrata)
Prenatal Diagnosis
Amniocentesis (1-2%)
– Amniotic fluid removed
Chorionic villus sampling (0.3%)
– Cells from the chorion (surrounds
ammnion)
Fetoscopy (2-10%)
– Direct visualization, removal of blood
from umbilical vein
Prenatal
diagnosis
cordocentesis
amniocentesis
Preimplantation
genetic diagnosis
Chorion villi
sampling
www.visembryo.com/baby/hp.html
Amniocentesis
Removal of about 20 ml of amniotic
fluid containing suspended cells
that were sloughed off from the
fetus
Performed during weeks 15-17 of
pregnancy
A few biochemical
analyses with some of the
amniotic fluid
Centrifugation
Quick determination of fetal
sex and analysis of purified
DNA
Biochemical analysis for the
presence of alleles that cause
many different metabolic
disorders
Fetal cells
Growth for
weeks in
culture
medium
Fig. 11.19, p. 186
Karyotype analysis
Sex Chromosomes
Discovered in late 1800s
Mammals, fruit flies
– XX is female, XY is male
Human X and Y chromosomes function
as homologues during meiosis
(In some organisms XX is male, XY female but for this
class XX is female and XY is male, no tricky stuff)
Sex Determination
eggs
sperm
X
Y
X
X
Female germ cell
Male germ cell
X
X
X
XX
XX
Y
XY
XY
sex chromosome combinations possible
in new individual
The Sex Chromosomes
The Y Chromosome
Fewer than two dozen
genes identified
One is the master gene
for male sex
determination
– SRY gene (Sexdetermining region
of Y)
SRY present, testes
form
SRY absent, ovaries
form
The X Chromosome
Carries more than 2,300
genes
Most genes deal with
nonsexual traits
Genes on X
chromosome can be
expressed in both
males and females
Pedigree
Chart that shows genetic connections
among individuals
Standardized symbols
Knowledge of probability and Mendelian
patterns used to suggest basis of a trait
Conclusions most accurate when drawn
from large number of pedigrees
The individual who needs genetical medical
consultation is called the proband O,
Proband tells to doctor medical history
about his disorder and any other affected
persons in the family. If this disorder
(disease) is inheritance, we can draw family
trees.
Pedigree symbols
Children marked under horizontal line
from left to right, in order of birth.
Members of the same generation are
placed on the same horizontal level.
Roman numbers are used for each
generation and Arabic numerals are
used to indicate each individual within
a generation.
Pedigree for Polydactly
female
I
male
II
III
*
1 2
3
IV
V
*Gene not expressed in this carrier.
4
5
Autosomal Recessive
Inheritance Patterns
If parents are
both
heterozygous,
child will have a
25% chance of
being affected
Galactosemia
Caused by autosomal recessive
allele
Gene specifies a mutant enzyme in
the pathway that breaks down
lactose
enzyme 1
LACTOSE
enzyme 2
GALACTOSE
+
glucose
enzyme 3
GALACTOSE-1PHOSOPHATE
GALACTOSE-1PHOSOPHATE
intermediate
in glycolysis
Autosomal
Dominant Inheritance
Trait typically
appears in
every
generation
Huntington Disorder
Autosomal dominant allele
Causes involuntary movements,
nervous system deterioration, death
Symptoms don’t usually show up until
person is past age 30
People often pass allele on before they
know they have it
Genetics Problem
A woman (hh) with normal nerve
physiology has a child with a man
(Hh) who will develop Huntington
Disease
What is the chance that the child
will have Huntington Disease?
Sex-Linked Genes
Is there a special pattern of inheritance for
genes located on the X chromosome or the
Y chromosome?
Because these chromosomes determine sex,
genes located on them are said to be sexlinked genes
Many sex-linked genes are found on the X
chromosome
More than 100 sex-linked genetic disorders
have now been mapped to the X chromosome
The human Y chromosome is much smaller
than the X chromosome and appears to contain
only a few genes
X-Linked Recessive
Inheritance
Males show
disorder more
than females
Son cannot
inherit disorder
from his father
A typical X-linked recessive
pedigree
X Linked Recessive Inheritance
Trait is much more common in males than females
An affected man passes the gene to all of his
daughters
A son of a carrier mother has a 50 % chance of
inheriting the trait
Male-to-male transmission never occurs
Carrier females are usually asymptomatic, but some
may express the condition with variable severity
because of Lyonization, or X-inactivation.
X-Chromosome Inactivation
Females have two X chromosomes, but males have
only one
If just one X chromosome is enough for cells in males,
how does the cell “adjust” to the extra X chromosome in
female cells?
The answer was discovered by the British geneticist
Mary Lyon
In female cells, one X chromosome is randomly switched
off
– That turned-off chromosome forms a dense region in the
nucleus known as a Barr body
– Barr bodies are generally not found in males because their
single X chromosome is still active
Barr body
X linked recessive, normal
father, carrier mother
carrier daughter
1 normal daughter
1 affected son
1 normal son
X linked recessive, affected
father
2 carrier daughters
2 normal sons:
Never any Male-toMale transmission!
Examples of X-Linked Traits
Color blindness
– Inability to distinguish among some of all
colors
Hemophilia
– Blood-clotting disorder
– 1/7,000 males has allele for hemophilia A
– Was common in European royal families
Royal Hemophilia Pedigree
Duchenne Muscular Dystrophy
Duchenne muscular dystrophy is a sex-linked disorder
that results in the progressive weakening and loss of
skeletal muscle
In the United States, one out of every 3000 males is
born with this condition
Duchenne muscular dystrophy is caused by a
defective version of the gene that codes for a muscle
protein
Researchers in many laboratories are trying to find a
way to treat or cure this disorder, possibly by
inserting a normal allele into the muscle cells of
Duchenne muscular dystrophy patients
Distribution of Mendelian disorders
68 % Autosomal dominant
26 % Autosomal recessive
6 % X-linked recessive
In a sex-influenced trait, an allele is dominant
in one sex but recessive in the other.
Hormonal differences can cause this
difference in expression.
For example, a gene for hair growth pattern
has two alleles, one that produces hair all
over the head and another that causes
pattern baldness. The baldness allele is
dominant (A) in males but recessive (a) in
females, which is why more men than women
are bald. A heterozygous male (Aa) is bald,
but a heterozygous female is not. The
genotype of a bald women is aa.
More Sex-Linked Recessive Inheritance
Male-pattern baldness
By age 50, nearly 60% of all men will experience some male
pattern baldness.
35 million Americans
experience some
degree of hair loss,
resulting in $900
million dollars a year
being spent in efforts
to grow it back.
Rogaine: only 5% actually grow
hair, 20-30% will have no effect,
X-Linked Dominant inheritance:
1) a trait affects mostly females;
2) if the affected female is heterozygous, she will pass the trait to
a half of her offspring (male and female);
3) an affected male passes the trait to his daughters.
Enamel hypoplasia (hereditary defect that cause
holes and cracks to appear around the crowns of the teeth)
is sex-linked dominant trait.
Y-Linked inheritance:
1) a trait affects only males;
2) father passes a trait to all sons.
Hairy pinnae (hairy ears) – Y-linked trait
Y-linked Ear-Hair
X
y
X
XX
Xy
X
XX
Xy
y = Ear Hair
Thank you
for attention !