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Human Genetics
Human Blood Groups
Blood type is determined by surface proteins called antigens
Two major types: ABO and Rh +/-
For example: A+ or O- blood
ABO Blood Types- controlled by multiple alleles and co dominated alleles
IA (A allele) codes for a A type protein
IB (B allele) codes for B type protein
i (O allele)
Rh Type
Rh is another surface protein
Having the Rh protein means your positive
Lack of Rh protein means your negative
A+ means they have the A antigen and Rh antigen
Alleles controlled by complete dominance
R=Rh positive r=Rh negative
RR=Rh+
Rr=Rh+
rr=Rh negative
Rh+ is more common than Rh-
Hemolytic Disease
Rh incompatibility between mom and child
ABO not an issue for incompatibility because the type of antibodies made for those markers are different and cannot cross placenta as easily
Can occur when a mom is Rh- and the fetus is Rh+
If some fetal cells mix with moms
can cause an immune reaction agfaist them and cause anemia in fetus
First brith is usually normal
Rhogam-treatment to prevent this now by injecting mother to kill any fetal cells in her bloodstream
Chromosomal Theory of Inheritance
1902: Walter Sutton
States that genes are located on chromosomes
Each gene occupies a specific place on each chromosome
Genes can exist in several forms called alleles
Gene LInkage
If genes are located on chromosomes and entire chromosomes are inherited together then groups of genes are passed on together
This some genes are linked and do not undergo independent assortment as Mendel stated
Thomas Hunt Morgan and Fruit Flies
Crossed purebred gray bodies and nromal wings with purebred black bodies and small wings
gray/normal are dominant traits
All F1 flies were grey/normal (GgNn)
Crossed F1 flies with homozygous recessive or (ggnn)
What would you expect?
25% Gray/Normal
25% Black/Normal
25% Gray/Small
25% Black/Small
Morgans Results
41.85% Gray/Normal
25% Black/Normal
41.5% Gray/Small
25% Black/Small
Lack of independent assortment pointed to genes bein glinked
Linkage groups are sets of inherited together (or genes on the same chromosome)
Why werent the genes always linked?
Answer: crossing over which produces new combinations of alleles or recombinants
More Morgan and Drosophilia
He worked with many mutants
Discovered a white eyed mutant-rare
Crossed his white eyed male with a normal red eyed female
The F1 results: 100% red eyed flies
F2 results: 75% red and 25% white BUT: all white eyes were male!
Conclusion: eye color allele is on the X chromosome thus it is sex linked
Sex Linked Traits
Any traits that are found on sex crhomosomes
Often called X linked because so few genes on the Y
Recessive sex linked traits are seen more often in males because they only have one X
Females have 2 Xs thus if they get an recessive allele on one they still have the other X as a back up
Recessive sex linked traties can be found in males
just not as often
Examples in humans: hemophilia and colorblindness
X Inactivation on Barr Bodies
Men have only one X functional in each cell because they also have a Y
Females have 2Xs but only one is active
Early on in embryonic development one X becomes randomly inactive in each embryonic cell
The inactive X is called a Barr body because of how it looks under the microscope
Inacgtive X becomes covered in a special type of RNA tpo inactive it
Some types of cat colors
Genetic Disorders
Most gventeic disorders are autosomal recessive because they make a mutant form of a protein that doesnt function properly
Can be autosomal dominant
sex linked recessive or sex inked dominant
Pedigrees can be used to track inheritance
Cystic fibrosis
Autosomal recessive
Most common genetic disorder among caucasians
Parents can be carriers and be unaware
Cl-ion channels do not function well
Mucous builds up on surface of tissues and organs
Prone to lung infections
Phenylketonuria (PKU)
Autosomal recessive
Lack enzyme for breaking down phenylabnine
Need a low phenylalaniene diet otherwise it can build up in brain and cause damage
Sickle Cell Anemia
Autosomal recessive
Mutation in hemoglobin gnee
RBCs can become stiff and sickle shaped
Most common symptom is pain-anywhere
Causes pain
swelling
HEterozygote advantage
Though the condition of sickle cell anemia is autosomal recessive the allele for sickle cells are codominant
HH is normal
hh is sickle cell anemia
Hh has some sickle cells but not too many
Sickle cell allele (h) is more prevalent in Africa than US
Provides protection against malria because sickle cells kill parasites
Huntingtons Disease
Autosomal dominant
Caused by mutation in a gene on chromosome 4
where CAG repeats
Excessive repeats cause3 an abnormal protein that blocks the function of the normal ones
Neurological symptoms; appear later in life
Sex linked Recessive Disorders
More common in males than females
Females can be carriers
Passed mother to son directly
Examples
Colorblindness
Hemophilia
Muscular dystrophy
Sex linked dominant exist tooo; hypertrichosis or werewolf syndrome
Hemophilai
Types A and B
Differ in mutatiojns that affect molecules in teh clotting cascade (factor VIII or IX)
Without one part of cascade clots cannot form
Common among royals because of intermarriage
Today: able to synthesize factors and inject
Colorblindness
The retina in the eye has light sensitive cells called rods and cones
Rods- light sensitive
Cones respond to different wavelengths (color) of light because of protein called opsin
3 main opsins: red
green
Mutations of colorblindness
Most mutations are red/green
Some people are missing entire red or green gene together
Fewer are blue/green
Not black/white vision typically
Colorblindness tests mix each color together
Duchennes Muscular Dystrophy
Characterized by enlargement of the muscles; degenerate over time
Gene for dystrophin is one fo the larges themes known of; 79 exons
Dystrophin protein si part of cytoskleton of muscle cells
Typical mutations cause premature translation termination (nonsense)
Becker MD is a milder form of the disase
Sex influenced Traits
Baldness
Alleles for baldness are influenced by the sex hormones
Therefroe
men and women exhibit baldness differently
Baldness allele acts dominant in men
but not in women
If expressed in women
usually after menopause
Pre-Natal Diagnosis
Diagnosis for a genetic disorder for an adult can be done with a blood sample
Prenatal diagnosis of a fetus can be done in 2 major ways”:
Amniocentesis (14-20 weeks)
CVS or Chormoic Vili Sampling (10-13 weeks)
CVS does not detect neutral tube defects like an amino
Gene Therapy
With all this information we are trying to find ways to not just treat these disorders but perhaps cure them
Gene theraphy is based in idea of trying to replace a bad copy of a gene with a good copy or normal copy
The challenge is finding a safe way to give the person a new gene; not as easy as it sounds!
We need a vector or vehicle to deliver the gene to the correct cells
first trials doen in 199 with a basic cold virus used; we added genes to the capsid
The patient died in 4 days from multiple organ failure; massive immune response
Scientists are working on new alternatives
Possible vectors
Various types of viruses; each with different sucesses for different reasones
Liposome: little bag of DNA surrounded by a lipid barrier
These can help give a godo copy of a gene for those that have one that doesnt function properly
What about Huntingtons? The good gene is already there
the bad one just interferes with it
Technique called RNAi developed
RNAi
Discovered by accidnet
as are many things in science
Cells have a system in place to protect against some vital infections
They recognize vital mRNAs and degrade them and any that look like them
including those normal ones in the cell
dsRNA is the type of RNA that catazlyzes this system to begin working
Pedigrees: What is a pedigree chart?
Specifically it is a diagram in which several generations of a family and the occurrence of certain genetic characteristics are shown
Pedigree charts show a record of the family of an individual
They can be used to study the transmission of hereditary contition
Determine the risk of passing on a genetic disorder to offspring
in addition to prenatal testing
They are particularly useful when there are large families and a good family record over several generations
Here are just some of the patterns of inheritance we discussed:
Autosomal dominant: Huntingtions
In a pedigree:
Affected are assumed to be heterozygous
All unaffected individauls are homozygous fo the normal recessive allele
Autosomal recessive: cystic fibrosis
sickle cell anemia
In a pedigree:
All affected are homozygous
Unaffected are assuend to be homozygous normal
Carriers may or may not be shown with a half shaded circle/square
Sex linked recessive: hemophilia
muscular dystrophy
In a pedigree:
Males get their X from their mother
Fathers pass their X to daughters only
Females express it only if they get a copy from both parents
Female carriers may or may not be shown with a half shaded circle
Expressed in males if present
Recessive in females
