Download Laws of Heredity -Single Gene Disorders

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Laws of Heredity - Single Gene Disorders
Mendel (1865), Experiments in Plant Hybridization - no
impact, paper essentially ignored, rediscovery in 1900
Mendel’s key idea: “elements” – now called genes are
the basic units of heredity. Laws based on observation.
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Mendel’s experiments:
In cross-pollinating plants that either produce
yellow or green peas exclusively, Mendel found
that the first offspring generation (f1) always has
yellow peas. However, the following generation
(f2) consistently has a 3:1 ratio of yellow to green.
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Mendel’s conclusions
1.
2.
3.
Inheritance of each trait is determined by "units"
that are passed on to descendents unchanged
(these units are now called genes)
An individual inherits one such unit from each
parent for each trait
A trait may not show up in an individual but can still
be passed on to the next generation.
In this experiment, the starting parent plants were
homozygous for pea color. The plants in the f1
generation were all heterozygous
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Mendel’s first law: the principle of
segregation
For any particular trait, the pair of
alleles of each parent separate and
only one allele passes from each
parent on to an offspring. Which
allele in a parent's pair of alleles is
inherited is a matter of chance.
We now know that this segregation of
alleles occurs during the process of sex
cell formation (meiosis).
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Mendel’s second law: principle of
independent assortment
Different pairs of alleles are passed to
offspring independently of each other.
The result is that new combinations of
genes present in neither parent are possible.
Today, we know this is due to the fact that
the genes for independently assorted traits
are located on different chromosomes.
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Family tree (pedigree)
Male
Female
Genes …
Alleles …
Mating
Parents
Children
Affected
Homozygous YY or GG
Heterozygous YG
Plomin, 2000 Fig 2.1 (Pg. 6)
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Practice …
Draw the family tree for a YY male and a GG female!
f1: all
heterozygotes!
heterozygotes!
Draw the family tree for a YG male and a YG female!
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The concept of dominance
With all of the seven pea plant traits that Mendel
examined, one form appeared dominant over the
other. Which is to say, it masked the presence of
the other allele. For example, when the genotype
for pea color is YG (heterozygous), the
phenotype is yellow.
However, the dominant yellow allele does not
alter the recessive green one in any way. Both
alleles can be passed on to the next generation
unchanged.
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Mendel’s Laws: SUMMARY
Law of Segregation: …alleles separate,
one allele passes from each parent …
Law of Independent Assortment alleles
pass independently of each other
Principles:
1.
2.
3.
Inherited features governed by a pair of
“elements”
One element inherited from each parent
Elements can dominate in their expression
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Terminology TODAY
Mendel’s “elements” are now called genes
Genes come in alternative forms, called alleles
Genotype – an individual’s combination of alleles
Phenotype – the observable trait
Homozygous – two copies of the same allele (AA, aa)
Heterozygous – one copy of each allele (Aa)
Mendelian diseases are diseases that are the result of a
single gene, they generally have a large effect on
behavior & distinctive patterns of familial transmission
Examples from psychiatry:
Genetic disorders with
Mendelian Patterns of
Inheritance
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Huntington’s Disease
Onset: mid-adulthood
Prevalence: 1 in every 20,000
Starts with: personality changes,
forgetfulness
Next 15-20 years: complete loss of motor
function and intellect
No treatment has been found to stop or
delay the decline
Consistent pattern of Heredity:
AUTOSOMAL DOMINANT
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Heredity of Huntington disease
Male
Draw the pedigree of a Huntington
disease family with one HD parent!
Female
Mating
Parents
Children
Affected
Plomin, 2000 Fig 2.1 (Pg. 6)
Affected individuals have one parent
with the disease, in the above case, the
affected parent is heterozygous. In this
case approx. half of the children
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develop the disease.
Phenylketonuria
Onset: early childhood
Prevalence: 1 in every 10,000
Severe problems in early neural development
leading to mental retardation
Due to disturbance in the metabolism of
phenylalanine (an essential amino-acid)
Treatment: special diet in early childhood lacking
phenylalanine
“Runs in families”, but typically NO affected
parents: AUTOSOMAL RECESSIVE
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Heredity of Phenylketonuria
Male
Draw the pedigree of a PKU family!
Female
Mating
Parents
Children
Affected
Carriers
Plomin, 2000 Fig 2.1 (Pg. 6)
PKU individuals do not typically have
parents with PKU. If one child has
PKU, the risk for other siblings is
25%. Parents are carriers in such cases.
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Color blindness
Most common form: red-green color blindness
(more frequent 8% in males)
SKIP-A-GENERATION PHENOMENON:
If mother is colorblind, & the father is not:
all of the sons but
none of the daughters
are affected!
However, half the daughter’s
sons are likely to be affected!
Consistent pattern of Heredity:
recessive allele on the X chromosome!
Sex-linked inheritance
Males are XY and females are XX
Two sex chromosomes are not genetically equivalent
(Y is about ¼ the size of the X)
Traits associated with genes
on the X chromosome
- X-linked
Traits associated with genes
on Y chromosome
- Y-linked
X-linked traits
Males
Females
One
X chromosome
Inherited from mother
Two possible genotypes
X+Y
XmY
Have trait/do not have trait
Hemizygous
Males
Two X chromosomes
Inherited from both parents
Three possible genotypes
X +X +
X +X m
XmXm
Heterozygotes are carriers of
recessive traits.
Females transmit their X
randomly to either their sons
or daughters
transmit their X to
their daughters, Y to their
sons
Males are more likely to be affected than females
regarding X-linked recessive traits
Color blindness: an x-linked
recessive trait
Male
Female
Draw the pedigree of a color blind
mother and an unaffected father!
cc
Mating
C
Parents
Children
c
cC
c
cC
Affected
Carriers
Heterozygotes for autosomal trait
X-linked carrier
Carrier of X-linked recessive trait
Plomin, 2000 Fig 2.1
Meiosis
Process of gametic cell production (gametogenesis) in which
genetic material is reduced by half (from diploid to haploid)
Problem!
Things can go wrong in meiosis:
e.g. nondisjunction of chromosomes: new egg and sperm
should have only member of each chromosome pair (haploid
set). When the division does not occur properly, an egg (or
sperm) may have both members of the chromosome
resulting in trisomy!
Chromosomal abnormalities responsible for
more than half of spontaneous abortions
(miscarriages)
Some fetuses with chromosomal anomalies survive,
though with developmental abnormalities
Most common: Down’s syndrome
Trisomy 21 - Down’s syndrome
Down’s syndrome
Clinical features: growth retardation, mental
retardation, distinct head and facial characteristics,
heart problems, premature aging
95% of the time, nondisjunction occurred in mother
1/1000 birth
increased rates with advanced maternal age (>35)
Nondisjunction is more likely to occur as female grows
older and activates immature eggs that have been
dormant for decades
Chromosome 21 is the smallest
Chapter 3 (pages 28-37)
Complex phenotypes
(depression, intelligence)
also seem to run in families,
but they don’t show
straightforward patterns
of inheritance
What’s going on?
Lifetime expectancy of Schizophrenia
Prevalence:
1/100
NO
consistent
pattern of
heredity:
morbidity risk
estimate:
Resemblance of Cognitive Ability (IQ)
NO
consistent
pattern of
Heredity:
correlation
increases
with genetic
relatedness
Complex, quantitative traits do NOT
violate Mendel’s laws!
IQ
height
pea size
schizophrenia
blood pressure
Single-locus
Completely Additive Model:
Genotype:
Phenotype:
A1 A 1
71”
A1 A2
70”
A2A2
69”
Single-Locus Phenotypic Distribution
A2A2
69”
A2A1
70”
A1A1
71”
Two-Locus Phenotypic Distribution
A2A1B2B1
A2A2B2B1
A2A2B2B2
68”
A2A1B2B2
69”
A2A2B1B1
A1A1B2B1
A1A1B2B2
A2A1B1B1
70”
71”
A1A1B1B1
72”
Three-Locus Phenotypic Distribution
67”
68”
69”
70”
71”
72”
73”
Infinite Number of Loci Model
Quantitative genetics
Polygenic Model: a quantitative phenotype is
influenced by many loci (genes) all of which have a
small (equal) and additive effect.
Types of Genetic Influence:
Monogenic (Single-gene, Mendelian)
Multigenic (polygenic, multifactorial)
Chromosomal
• Mendel's experiments and laws of heredity
• Family trees of
– autosomal dominant (Huntington’s)
– autosomal recessive (Phenylketonuria)
– and x-linked traits.
• Chromosomal anomalies - Down's syndrome
• Complex traits and quantitaive genetics
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Selected readings
Textbook:
Ch 2. pg. 6.-12.
Ch 3. pg. 20.-25. and pg. 28.-37.
The outline from this lecture presentation
will be available at the course website:
Practice for exam:
Draw the pedigree of a color blind father
and an unaffected (non-carrier) mother!
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4 Sex-Linked Traits:
NORMAL:
A: 29, B: 45,
C: --, D: 26
Red-Green mix:
A: 70, B: --,
C: 5, D: -Red blind:
A: 70, B: --,
C: 5, D: 6
Green blind:
A: 70, B: --,
C: 5, D: 2
http://waynesword.palomar.edu/colorbl1.htm