Transcript Ch. 5- complex Genetics thru Mitochondrial DNA

Ch.5 Beyond Mendel’s Laws
5.1
Lethal Alleles
 Lethal genotypes- death before alleles are
passed on.
 Before reproduction.
 Exception- Huntington’s disease Begins at age 30-40.
 Lethal alleles- spontaneous abortions
 If both parents are heterozygous 25 % chance of being homozygous recessive.
 Homozygous dominant- lethal in embryos
 Ex. Mexican hairless dogs.
Incomplete Dominance
 Heterozygous phenotype is intermediate
between each homozygote.
 Human Ex.
 TaySachs- intermediate enzyme level in
heterozygotes.
 Human hair curliness
 SS=straight, ss=curly, Ss=wavy
 FH-Familial hypercholesterolemia
 A heterozygote has half the number or
receptors for LDL cholesterol in the liver with
intermediate plasma cholesterol levels.
Classic Snapdragons
 use C= color
 RR= Red CRCR
 rr= white(WW); CWCW
 Rr (RW)= pink; CRCW
 P1
F1
F2
CRCR x CWCW
CRCW x CRCW
CRCR CRCW CWCW 1:2:1
red
pink
white
Same genotypic and phenotypic
ratios
Codominance:
 Both alleles are experessed in a
heterozygote.
 AB Blood Type
 ABO Blood types:
 Determined by cell surface antigens
 Antigen- protein with attached sugar on plasma
membrane of red blood cells
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
Type
Type
Type
Type
A- A antigen
B- B antigen
O- no sugar antigen
AB- both A and B antigens
Codominance examples Both alleles are expressed equally
 Example is red and white striped flowers
 Roan cattle
Multiple alleles
 1 gene; more than 2 allele forms
 Examples Acyl CoA dehydrogenase deficiency
 Mitochondria- affects heart and skeletla
muscles.
 Other alleles lessen severity producing some
enzyme.
 PKU- buildup of phenylalanine
 More than 300 mutant alleles-4 phenotypes
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Classic PKU- profound mental retardation
Moderate PKU
Mild PKU
Excrete excess phenylalanine in urine
Correlation of genotypes with phenotypes – to
monitor diet and predict outcome.
Cystic Fibrosis



Several hundred alleles
70% of cases- F508 homozygous
Many variations
Pancreatic function correlates better
than lung symptoms.
Blood types
 Phenotypes- Blood
Types (4)
A
B
AB
O
 Genotypes (6)
IAIA or IAi
IBIB or IBi
IAIB
ii
Blood Typing:
 ABO blood group:
 Antigens are on the rbcs.
 Antibodies to other antigen sugar types circulate in
the plasma portion of blood.




Blood
Blood
Blood
Blood
Type A- has anti B in plasma.
Type B- has anti A in plasma
Type O- has anti A,B in plasma
type AB- no anti A or anti B
 Blood Type O- universal donor because there are no A
or B antigens.
 Blood type AB- universal recipient, since no
antibodies to A or B.
 To type a person’s blood- the rbcs are mixed with
different antibody sera. Clumping indicates the
presence of the corresponding antigen on the red
blood cells. Ex Antigen A clumps with antiA sera.
Rh Factor Named for rhesus monkeys where found.
 The main factor is a D antigen found on the red blood
cells.
 Unlike ABO blood types, antibodies are only present if
an Rh negative person is exposed to Rh positive blood
cells.
 85 % pop. Has the D allele=Rh +
 15% pop. Is recessive dd= Rh Rhogam- anti D is given to Rh- mothers to bind any
fetal Rh + red blood cells if there is a bleed to prevent
the mom from making circulating antibodies to the
fetus’ red blood cells.
 Hemolytic Disease of the newborn results from this
imcompatibility. – can result in death.
Epistasis
One gene affects the expression of a second gene
Example: H gene is epistatic to the ABO gene.
• H protein attaches a molecule to the cell surface
to which the A or B antigens are attached
• hh genotype = no H protein=
• Without H protein the A or B antigens can not be
attached to the cell
• All hh genotypes have the phenotype of type O,
although the ABO blood group can be
anything (A, B, AB, or O)
Bombay phenotype-identified in
1952- Bombay, India
 Very rare example of epistasis
 Individuals phenotype= Blood type O
 However they have no H antigen so they
have antibodies to H (anti-H), antibodies to
A (anti-A) antibodies to B (anti-B) in their
circulating plasma.
 Bottom line- they will be incompatible with
all blood types; even O
 Can only receive their own blood; or
another Bombay’s.
Incomplete Penetrance
 The phenotype is not always observed
among individuals carrying the genotype
– express or not
 DD or Dd - only 80% show polydactyly
Variable Expressivity
• A phenotype that varies in intensity
 Polydactyly two extra digits on each hand and foot
vs. one extra digit on one foot
 Individuals with the same genotype for familial
hypercholesterolemia have varying levels of
symptoms
Pleiotropy
One gene has many
symptoms
or controls several functions
Example: porphyria
variegata
Figure 5.5a
Figure 5.5b
Photo © North Wind Picture Archives
Genetic Heterogeneity
• Different genes can produce identical phenotypes
 Hearing loss
 Osteogenesis imperfecta
• Genes may encode for different enzymes in a
biochemical pathway
 Clotting disorders
Phenocopy
 Appears inherited but is caused by the
environment
 May have symptoms that resemble an inherited
trait or occur within families
Examples:
 Exposure to teratogens
 Thalidomide causes limb defects similar to
inherited phocomelia
 Hydroquinone exposure looks like
alkaptonuria
 Infection
 AIDS virus can be passed from mother to
child, looking like it is inherited
Importance of Human Genome
Sequence
 Complications to Mendelian
inheritance more common than
originally thought
 Overlapping of definitions –
Marfan syndrome has both
epistasis and genetic
heterogeneity
Table 5.3
Mitochondrion
 Organelle providing cellular energy
 Contains small circular DNA
 No crossing over or DNA repair
 High exposure to free radicals
 Mutation rate is greater than nuclear DNA
 37 genes without noncoding sequences
 Mitochondrial genes are transmitted from
mother to all of her offspring
Mitochondrial
Inheritance
Figure 5.8
Mitochondrial DNA
pedigree
Mitochondrial Disorder Examples
 Mitochondrial myopathies – weak
muscles
 Leber optic atrophy – impairs
vision
 Ooplasmic transfer technique can
enable woman to avoid
transmitting a mitochondrial
disorder
Heteroplasmy
Many copies of the mitochondrial
genome per cell
May have more than one allele for
the same gene in the same cell
Heteroplasmy is the condition where
mitochondrial DNA sequence is not
the same in all copies