Transcript Fundamentals of human genetic

Theme: Fundamentals
of human genetic
Plan of lecture:
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Introduction to Genetics and heredity
Gregor Mendel – a brief bio
Genetic terminology
Monohybrid crosses
Patterns of inheritance
Dihybrid crosses
Test cross
Gene interactions
Introduction to Genetics
• GENETICS – branch of biology
that deals with heredity and
variation of organisms
• Chromosomes carry the hereditary
information (genes)
• Arrangement of nucleotides in DNA
• DNA  RNA  Proteins
Gregor Johann Mendel
• Austrian Monk, born in what is now
Czech Republic in 1822
• Son of peasant farmer, studied
Theology and was ordained
priest Order St. Augustine.
• Went to the university of Vienna,
where he studied botany and learned
the Scientific Method
• Worked with pure lines of peas for
eight years
• Prior to Mendel, heredity was
regarded as a "blending"
process and the offspring were
essentially a "dilution"of the different
parental characteristics.
•Mendel looked at seven traits or characteristics of
pea plants
• In 1866 he published
Experiments in Plant
Hybridization, (Versuche über
Pflanzen-Hybriden) in which he
established his three Principles of
Inheritance
• He tried to repeat his work
in another plant, but didn’t
work because the plant
reproduced asexually! If…
• Work was largely ignored for
34 years, until 1900, when
3 independent botanists
rediscovered Mendel’s work.
• Mendel was the first biologist
to use Mathematics – to
explain his results
quantitatively.
• Mendel predicted
The concept of genes
That genes occur in pairs
That one gene of each pair is
present in the gametes
Genetics terms you need to know:
• Human genetics is the science that
learns the peculiarities of the
hereditary and variability in human
organism
• Heredity – is the transmission of
characteristics from parent to
offspring through the gametes
Genetics terms you need to know:
• Inheritance – is the way of passing of
hereditary information which depends on
the forms of reproduction
During asexual reproduction the main
traits are inherited through spores or
vegetative cells, that's why the maternal
and daughter cells are very similar.
During sexual reproduction the main
traits are inherited through gametes.
Genetics terms you need to know:
Gene – a unit of heredity; a section of DNA
sequence encoding a single protein
Genotype – is the genetic constitution of
an organism (a diploid set of genes)
Genome – is a collection of genes of an
organism in sex cells (a haploid set of
genes)
Alleles – two genes that occupy the same
position on homologous chromosomes
and that cover the same trait (like
‘flavors’ of a trait)
Locus – a fixed location on a strand of
DNA where a gene or one of its alleles is
located
Genetics terms you need to know:
Homozygous – having identical genes (one
from each parent) for a particular
characteristic.
Heterozygous – having two different genes
for a particular characteristic.
Dominant – the allele of a gene that masks
or suppresses the expression of an
alternate allele; the trait appears in the
heterozygous condition.
Recessive – an allele that is masked by a
dominant allele; does not appear in the
heterozygous condition, only in
homozygous.
Dominant allele is symbolize with a capital
letter
Recessive allele is symbolize with the
corresponding small letter
If both alleles are recessive, the individual is
homozygous recessive aa
An individual with two dominant alleles is
homozygous dominant AA
An individual with Aa alleles is a
heterozygote
• Genotype – describes the organism’s alleles (the
genetic makeup of an organisms)
• Phenotype – the physical appearance
of an organism (Genotype + environment)
• Monohybrid cross: a genetic cross involving a
single pair of genes (one trait); parents differ by
a single trait
P = Parental generation
F1 = First filial generation; offspring from a
genetic cross
F2 = Second filial generation of a genetic cross
Monohybrid cross
• Parents differ by a single trait (stem size)
• Crossing two pea plants that differ in stem
size, one tall one short
T = allele for tall
t = allele for dwarf
TT = homozygous tall plant
t t = homozygous dwarf plant
P ♀T T  ♂t t
Monohybrid cross for stem length:
P = parentals
true breeding,
homozygous
plants:
F1 generation
is heterozygous:
TT  tt
(tall)
(dwarf)
Tt
(all tall plants)
Punnett square
• A useful tool to do genetic crosses
• For a monohybrid cross, you need a square
divided by four….
• Looks like
a window
pane…
We use the
Punnett square
to predict the
genotypes and
phenotypes of
the offspring.
Punnett square
•
"split" the letters of the genotype for each
parent & put them "outside" the p-square
• determine the possible genotypes of the
offspring by filling in the p-square
• summarize results (genotypes & phenotypes of
offspring)
T
TT  tt
t
t
Tt
Tt
T
Tt
Genotypes:
100% T t
Tt
Phenotypes:
100% Tall plants
1. The law of monotony of the first filial
generation
A - yellow seed; a - green seed
P:
♀ AA x ♂ aa
G (Gametes): A
a
F1:
Aa (yellow)
During crossing two homozygous which are differ
from each other by one trait all progeny in the
first filial generation is monogyny as well as
phenotypic and genotypic
2. The law of segregation
A cross between plants obtained from F1 plants.
P:
♀ Aa
x
♂ Aa
G:
A, a
A, a
F2 : AA; Aa; Aa; aa
From a pair of contrasting characters (alleles)
only one is present in a single gamete and
in F2 these characters are segregated in the
ratio of three to one (3:1) by phenotype and
1:2:1 by genotype.
When gametes are formed in heterozygous diploid
individuals, the two alternative alleles segregate
from one another.
• Getting all yellow seeds was an interesting
result in itself
• Having viewed these results, Mendel then let
the F1 generation, was 6022 yellow seeds
and 2001 green seeds.
Two things stand out.
• green seeds disappeared in F1, but come
back in F2.
• green seeds came back in F2 as a specific
proportion of the seeds as a whole.
• Today, we know that inheritance occurs
by way of gametes, and that it is due to
meiosis that each gamete carries only
one factor for each trait.
• Today, we know that the genes within the
gametes are unaffected by the somatic
cells.
• Mendel's law of segregation is in keeping
with a particulate theory of inheritance
because individual and separate factors
are passed on from generation to
generation.
• It is the reshuffling of these factors that
explains how variations come about and
why offspring differ from their parents.
Human case: CF
• Mendel’s Principles of Heredity
apply universally to all
organisms.
• Cystic Fibrosis: a lethal genetic
disease affecting Caucasians.
• Caused by mutant recessive gene
carried by 1 in 20 people of
European descent
• CF disease affects transport
in tissues – mucus is
accumulated
in lungs, causing infections.
Inheritance pattern of CF
If two parents carry the recessive gene of
Cystic Fibrosis (c), that is, they are
heterozygous (Cc), one in four of their
children is expected to be homozygous for cf
and have the disease:
CC = normal
Cc = carrier, no symptoms
cc = has cystic fibrosis
C
c
C
CC
Cc
c
Cc
cc
Dihybrid crosses
• Matings that involve parents
that differ in two genes (two
independent traits)
For example, flower color:
P = purple (dominant)
p = white (recessive)
and stem length:
T = tall
t = short
Dihybrid cross: flower color and
stem length
TT PP  tt pp
(tall, purple)
Possible Gametes for parents
T P and t p
(short, white)
tp
TP TtPp
TP TtPp
tp
TtPp
TtPp
F1 Generation: All tall, purple flowers (Tt Pp)
Dihybrid cross F2
If F1 generation is allowed to self pollinate,
Mendel observed 4 phenotypes
Tt Pp  Tt Pp
(tall, purple)
Possible gametes:
TP Tp tP tp
TP
(tall, purple)
Tp
tP
TP TTPP TTPp TtPP
Tp TTPp TTpp TtPp
tp
TtPp
Ttpp
TtPP
TtPp
ttPP
ttPp
tp TtPp
Ttpp
ttPp
ttpp
tP
Four phenotypes observed
Tall, purple (9); Tall, white (3); Short, purple (3); Short white (1)
Dihybrid cross: 9 genotypes
Genotype ratios (9):
Four Phenotypes:
1
TTPP
2
TTPp
Tall, purple (9)
2
TtPP
4
TtPp
1
TTpp
Tall, white (3)
2
Ttpp
1
ttPP
Short, purple (3)
2
ttPp
Short, white (1)
1
ttpp
Principle of Independent Assortment
• Based on these results, Mendel
postulated the
3. Principle of Independent
Assortment:
“Members of one gene pair
segregate independently from other
gene pairs during gamete formation”
Genes get shuffled – these many
combinations are one of the advantages
of sexual reproduction
Relation of gene segregation to
meiosis…
• There’s a correlation between the
movement of chromosomes in meiosis
and the segregation of alleles that
occurs in meiosis
Beyond Mendelian Genetics:
Incomplete Dominance
Mendel was lucky!
Traits he chose in the
pea plant showed up
very clearly…
One allele was dominant over another, so
phenotypes were easy to recognize.
But sometimes phenotypes are not very
obvious…
Incomplete Dominance
Snapdragon flowers come in many colors.
If you cross a red snapdragon (RR) with a white
snapdragon (rr)
RR
You get PINK flowers (Rr)!
 rr
Genes show incomplete dominance
when the heterozygous phenotype
is intermediate.
Rr
Incomplete dominance
When F1 generation (all pink flowers) is self
pollinated, the F2 generation is 1:2:1
red, pink, white
Incomplete Dominance
R
r
R
r
R R
Rr
Rr
rr
Codominance
Genotype
Phenotype
LMLM
M
LMLN
MN
LNLN
N
• Both alleles are equally
dominant
• Heterozygotes express both
alleles = distinct
expression of the gene
products of both alleles
can be detected
• MN blood group
• F2 genotype and
phenotype ratios are 1:2:1
Multiple Alleles
• Genes can be characterized by more than 2
alleles
• Multiple alleles (>2) can be studied only in
populations, because any individual carries
only 2 alleles at a particular locus at one time
• ABO blood groups
– Each individual is A, B, AB, or O phenotype
– Phenotype controlled by isoagglutinogen
marker on RBC
– IA and IB alleles are dominant to the IO
allele
– IA and IB alleles are codominant to each
other
Phenotype
Possible
Genotype
Antigen
on RBC
surface
Antibody
Made in
Plasma
A
IAIO, IAIA
A
Anti-B
B
IBIO,IBIB
B
Anti-A
AB
IAIB
AB
Neither
O
IOIO
O
Both
Importance of A, B, O blood group antigens in
medicine
Transfusion compatibility
Blood type:
AB
A
B
O
Donate to:
AB
A or AB
B or AB
O, A, B, AB
•Disease resistance
Resistance to cholera and other types of infant
diarrhea:
AB > A > B > O
•Possible resistance to other diseases: malaria,
syphillis, cancer
Continuous variation
• Continuous variation (polimery).
Different dominant non-allele's genes
affect on one trait, making it more
expressive.
• Traits determined by more than one
gene are polygenic - meaning "many
genes" - or quantitative traits.
Continuous variation
• Usually, several genes each contribute to the
overall phenotype in equal, small degrees.
• The combined actions of many genes
produce a continuum, or continuously
varying expression, of the trait.
• Example: Skin color is familiar example of
polygenic trait in humans.
Skin color is quantitative trait, that are controlled by two
pairs of genes A1a1, A2a2.
Let’s sign skin color as
• A1A1A2A2 – very dark
• A1A1A2a2 or A1a1A2A2 — dark
• A1a1A2a2 — medium brown
• A1a1a2a2 or a1a1A2a2 — light
• a1a1a2a2 — white (pale skin).
TASK
A woman with white skin married a
medium-brown man. What is the skin
color possible for their children?
P: ♀a1a1a2a2  ♂ A1a1A2a2
G: a1a2
A1A2, A1a2, a1A2, a1a2
F1: A1a1A2a2; A1a1a2a2; a1a1A2a2;
a1a1a2a2
Pleiotropy
• Often an individual allele will have more than
one effect on the phenotype.
• Such allele is said to be pleiotropic.
• Pleiotropic relationships occur because in
examine the characteristics of organisms; we
are studying the consequences of the action of
products made by genes.
• Pleiotropy occurs in genetic diseases that affect
a single protein found in different parts of the
body. This is the case for Marfan syndrome.
Marfan syndrome
•
Autosomal dominant defect
in elastic connective tissue
protein called fibrillian
• Fibrillian is abundant in the
lens of the eye, in the aorta,
and in the bones of the limbs,
fingers, and ribs
• Marfan syndrome symptoms
include lens dislocation, long
limbs, spindly fingers, and a
caved-in chest
“He who likes to eat fruit
must climb the tree”
(English proverb)
Thank you for attention !