Mutations that convert amino acid-coding codons into (premature) stop codons. Will produce a null allele where you do not express a protein from that allele.
Mutations convert an amino acid codon into a codon for a different amino acid. Most likely to inherit these mutations paternally.
Mutations that alter the codon sequence but NOT the amino acid. It will change the stability. Different codon sequence but it codes the same amino acid.
Convert a normal stop codon into an amino acid codon (Hemoglobin Constant Spring in the alpha-globin gene). The ribosome will not stop where it is supposed to knocking the RNA binding off making the RNA less stable.
May change the reading frame (frameshift mutation) resulting in changes in the amino acid sequence, if the number of bases deleted/inserted is not a multiple of three.
Insertion or Deletion Mutations
Purine (AG) for Purine or Pyrimidine for Pyrimidine (CT)
Purine for Pyrimidine
Stretches of DNA consisting of 2,3,4 nucleotide repeats, that are polymorphs-STRP.
Repeated 10 to a few dozen times. Seen via PCR and gel electrophoresis.
Insertions in tandem of varying numbers- usually 100s-1000s of DNA sequences 10-100 base pairs in length. Seen on a Southern Blot.
Have only Anti B antibodies and are there for incompatible with Type B blood.
Have only Anti A antibodies and are therefore incompatible with type A blood groups.
Are compatible with A, B, AB, O because they have no anti-antibodies. Therefore these are universal acceptors.
Have both Anti A and Anti B antibodies and are therefore incompatible with A, B, AB.
This blood group is a universal donor.
Is a recessive trait, MUST be homozygous, meaning both Anti A, and Anti B Abs so they are universal donors.
Has no serum antibodies, that is why they are universal recipients.
Produced by 1 gene, with 3 alleles on Chromosome 9q
ABO Blood Groups
Allele produces glycosyltransferase, adds N-acetylgalactosamine to H antigen
Different allele adds D-galactose to the H antigen
4 nucleotides, change 4 amino acids in the transferase.
Difference between A and B alleles
Different allele DOES NOT produce a functional transferase, so there is no sugar added to H antigen.
Due to a frameshift mutation that eliminates transferase activity results in no A or B transferase.
Produces RhD Ag on RBC membrane, encoded by RHD gene on Chromosome 1
Dad is Rh+ and Mom is Rh- and the fetus is Rh+. During birth mom is exposed to Rh+, and develops Anti Rh+ Ab. Now Mom has Anti Rh+ Ab. So in a second pregnancy the fetus is again Rh+ and IgG Ab crosses the plcenta and cause RBCs of fetus o lyse leads to anemia in the fetus (apparent when the child is born).
Hemolytic Disease of the Newborn
What is the treatment for Hemolytic Disease of the Newborn?
Give the Rh- mother injections of anti-Rh Ab (RhoGAM), do destroy fetal erythrocytes in the mother's blood.
When do you give the mother RhoGAM?
At 28 and 32 weeks of gestation w/in 72 hours of childbirth.
On every nucleated cell , not expressed in RBCs because they are not nucleated. contain 2 polypeptide subunits that have a variable alpha chain, encoded with MHC. Present endogenous protein Ags. Nonpolymorphic peptide leading to B2 microglobulin.Displays Ag to Cytotoxic T-cells (CD8+)
MHC class I
Transports peptides into the ER
Large multifunctional protease (proteosome LMP). Contains DM, TAP, DP, DQ, and DR. Deals with exogenous antigens
MHC class II
How is Ii removed?
Mosto common enzyme deficiency dealing with MHC class III. Leades to congential adrenal hyperplasia and female pseudohermaphroditism.
21-OH (21 Hydroxylase)
Chronic inflammatory disease of the spine and sacroiliac joints. It is an autoimmune disorder. Positive in 9% of all Norwegians with this disease.
HLA-B27 (MHC class 1 molecule)
Autosomal recessive disease due to a mutant HFE gene (cys-tyr) in linkage disequilibrium with HLA-A*0301. This mutation leads to iron overload and they must have a homozygous mutation in this HFE gene (involved in iron transport or metabolism of the intestine).
Primary susceptibility alleles are DQB1 (class II), which segregate with HLA-DR3 and HLA-DR4 (coinherited).
Type 1 Diabetes
Are primary determinants of transplant tolerance and graft rejection.
Measures the proportion of chromosomes that contain a specific allele (gene).
Allele Frequency (Gene Frequency)
Measures the proportion of each genotype in a population (how the alleles are distributed among homozygotes and heterozygotes).
How is the allele frequency calculated for the recessive allele?
(2x # of homozygotes) + (1x # of heterozygotes) / (2 x total population)
If for a particular locus there are 2 alleles (A &B) in the population, and the frequency of allele A is 40%, that of allele B must be 60%, so that the frequency of A +B is?
The wild type allele (normal)
What is p^2?
Homozygous normal genotype
The mutant allele
What is q^2?
Homozygous mutant allele
The heterozygous genotype
Population is large and matings are random, allele frequencies remain constant over time because there is no appreciable rate of mutation. All genotypes are equally capable of mating and passing on their genes, i.e, there is no selection against any particular genotype. No significant immigration of individuals from a population with allele frequencies very different from the endogenous population.
Hardy Weinberg Law Assumptions
What is the equation for autosomal recessive diseases?
q= square root of I
What is the equation for autosomal dominant?
q= 1/2 x I or I=2q
What is the equation for X-linked recessive?
After finding q, how do you calculate the carrier frequency (2pq)?
What are factors that disturb Hardy Weinberg Equilibrium?
stratification, assortative mating, consanguinity, mutation and selection, genetic drift, and genetic flow.
Cell surface receptor (also for HIV). This allele has a 32bp deletion which leads to a frameshift and the receptor will not work. Confers resistance for HIV. A high percentage of these alleles are found in Ashkenazi Jews, in Iceland and the British Isles. My have been a heterozygote advantage against the bubonic plague.
CCR5 Cytokine Receptor Gene
Loss of genetic variation that occurs when a new population is established by a very small number of inidividuals from a larger population. Stratification ex: Amish
Mutant EVC or EVC2 genes. Results in congenital heart defects (most commonly atrial septal defect-60% of individuals). Post axial polydactyly, prenatal tooth eruption, fingernail dysplasia, short limbed dwarfism, fusion of the hamate and capitate bones (wrist bones).
Ellis- van Creveld Syndrome
What are examples of the Heterozygote Advantage?
Cystic Fibrosis against Cholera and Sickle Cell Disease against Malaria.
What genes are implicated in Chron's Disease?
exons of the NOD2 gene
Bind gram (-) bacteria, participates in the inflammatory response by turning on NF-kB transcription factor, these variants are most common in Caucasian patients with IBD.
NOD2 (Crohn's Disease)
Occurs anywhere in the digestive tract (mostly the ileum or ascending colon). Presents with nocturnal abdominal pain, frequent diarrhea, and weight loss. There is an increased risk of adenocarcinoma of the intestine in long-standing CD. There is not cure but corticosteriods are often used to lower the inflammation. Also presents with erythema nodosum, pyoderma gangrenosum, and primary sclerosing cholangitis
Inflammatory disorder that involves tender, red bumps- under the skin can become purplish-brown.
Large, painful ulcers on the skin they mostly develop on the legs.
Chronic liver disease by progressive inflammation and scarring of the bile duct. This impedes the flow of bile leading to cirrhosis, liver failure, or cancer. At this point a liver transplant may be necessary.
Primary sclerosing Cholangitis (PSC)
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