autosomal dominant

1 in 10,000; all race and gender

4p16

IT-15 gene-defectivev gene alters Hungtington protien

CAG repeats, less than 29= normal, 29-35= borderline and 36-121= full blown disease

100% penetrance, DNA sequenceing for positive identification

Cystic Fibrosis

Autosomal recessive

affects breathing and digestion, 30,000 cases in US

Affects the normal movements of salt into and out of cells especially in cells that lings the lungs resulting in mucus sticky buildup and secretions. Mucus clogs the lungs and leads to breathing problems. This leads to infection and evevntually collapse of the lungs

CFTR gene

over 1300 known mutation, DNA sequencing

common inherited of mental retardation, 1in 4000 males and 1 in 8000 females. Varying degrees of mental retardation

FMR-1 gene located on Xq27.3

CGG repeat, normal= 5-44; carriers= 59-200 and fully affected= 200+

continued repeats causes abnormal Methylation of the CpG sites within the repeat sites, resulting in the silencing of the gene, DNA sequencing

mutation in the dystrophin gene

located on X chromosome

muscle degeneration

point mutation, deletion, duplication

most common hereditary blood coagulation disorder in US

Increases risk for venous thrombosis 3-8 fold for heterozygous

Increases risk for venous thrombosis 30-140 fold for homozygous

Complications aside from venous thrombosis include pulmory embolism and arterial clots

Hypercoagulability test

activated protein C (APC) resistance testing used for screeng factor V leiden

If resistance is present, it is usually followed by gene testing for Factor V Leiden for detemination of heterozygous or homozygous

Base chagne at 1691 of G>A

2nd most common inherited clotting disorder

2% general population is heterzygous

mild risks for clots

sequencing can reveal genotype. Mutation diagnostic must be done with genetic testing

check for heterozygous or homozygous

Most common form of iron overload disease. This causes the body to overload iron and stored throughout the body in organs and tissues causing damage overtime

Autosomal recessive disorder, HFG gene which regulate the amount of iron absorbed from food

Heterozygous will not develop disease except with slightly elevated iron absorption

1 out of 8 is carrier

symptoms include join pains, abdominal pain, lack of energy

two HFE gene mutation (C282Y and H63D) associated with hemochromatosis

genetic test offer detecting rate about 87% for Hereditary hemochromatosis therefore, genetic is determined whether or not someon is a carriers

measure HIV-RNA, several viral load tests exist but only 2 are approaved for general use

Amplicon HIV-1 monitor test (PCR method)

NucliSens HIV-1 QT (NASBA method)

both approaved by FDA

Chiron company used bDNA technique, on the verge of getting FDA approval

result are usually given as number of HIV RNA copies/ ml of blood

result can be given in number of which must multiply by 1000

less tha 20,000 count is consider low risk

between 20,000-2,000,000 has much higher chance

above 200,000 has 24% of disease progression

new ultra-sensitive PCR test count as low as 50 copies of HIV RNA in blood

qualitative PCR test is most sensitive,

anything below 100 eq/ml is consider negative

quatitative PCR can detect up to 200 eq/ml

bDNA technique detect only 200,000 eq/ml not sensitive

gastric tumors have been linked with the presence of EBV

Burkitt's lymphoma has been associated with EBV

Post-transplant lymphoproliferative disorder-uncontrolled lymphatic tissues

Immunocompromised individuals are at high risk for B cell lymphoproliferative disorders from proliferation to lymphoma

can be measured via viral load on peripheral blod

real-time quantification on EBV can be done for early diagnostic

detect rearrangements of the immunoglobulin heavy chain or TCR gene using PCR

IgH-blood or bone marrow samples

IgH gene rearrangement is consistent with clonal proliferation of B lymphoid cells

Clonal IgH expansion is indicative of leukemia or lymphoma

IgH is the first rearranged Ig gene in B cell development followed by light chain genes, kappa and lambda chain rearrangment after heavy gene rearrangment

can be used to detect minimal residual disease post-treatment

specific tumor marker

TCR-blood, bone marrow or paraffin embedded samples

Philadelphia chromosome (ph) is diagnosis in 95% of CML cases and subset in ALL

Detection is by genomic Southern hybridization for CML

more sensitivity detection looking at t(9;22) in ALLs with different breakpoints, use RT-PCR method

isolation RNA so sample must be delivered within 1 hour

specific junction fragment detected by RT-PCR defines the pattern of exons joined as a result of translocation event

Only speciment with BCR-ABL translocation will product these fragment

BCRb3-ABLa2= 200 bp>> CML&p210 protein, bcr13

characteristic of 90% cases in follicular lymphoma

translocation juxtaposes the BCL2 gene on 18q21 and enhancer region of the IgH gene from chromosome 14q32

this result in abnormal expression of BCL2 protein product in mature B lymphoid cells

BCL2 DNA fragment is used as diagnostic marker for MRD

chromosome translocation junction fragment detected by gel electrophoresis in size from 100 to 600 bp and involve 1 of 2 possible BCL2 regions. MBR (major breakpoint region) and mcr, minor cluster regions are the sites of approximately 65% and 25% of BCL2 breakpoint.