Patho-genetic screening (Exam 1, Fall 2022)
Chromatin
located in cells nucleus and contains chromosomes
Chromosomes
contain genes, basic units of inheritance
Genes
composed of DNA and histones that cause DNA to coil into tightly compressed structure
Genetic testing
helps to determine whether an individual carries specific disease-causing mutations
Carrier screening
identify heterozygous carriers for many recessive diseases
-CF
-Sickle cell
-Tacy-Sachs
helpful for reproductive decisions
-especially in populations where diseases are common
prevalence of some diseases have declined d/t increase in screening
If the carrier is positive (usually mom) then the
partner will undergo testing, even more complex testing
Amniocentesis
withdrawal of small amount of amniotic fluid from uterus @ 16 wks gestation
fetal cells within fluid cultured and karyotypes to detect chromosome abnormalities
low risk of fetal loss
What can be detected as an elevation of alpha fetoprotein level in amniotic fluid?
neural tube defects
spina bifida
anencephaly
Chorionic villus sampling (CVS)
extraving small amount of villous tissue (from placenta) from chorion @ 10-12 wks
doesn't require in vitro cell culturing for chromosome analysis
sufficient numbers directly available in tissue
higher fetal loss than amniocentesis
Preimplantation genetic diagnosis (PGD)
carried out on early embryos (8-12 cells) created by in vitro fertilization
1-2 cells removed from embryo (no damage) and cells tested for chromosome
abnormalities or single-gene disorders
, genetic disorder found=not implanted
Analysis of Fetal DNA in maternal circulation
6-8 wks gestation - fetal cells + cell-free fetal DNA can be found in mother's
bloodstream
-tested for disease-causing mutations
advantages: early dx and minimal risk to mother and fetus
rapidly cleared by renal system (16 hr 1/2 life)
Analytes
screening routine by measuring maternal serum samples
B-hCG + PAPP-A
+
nuchal translucency US
assess risk of conditions
-trisomies 21, 13, 18 + neural tube defects
does not evaluate DNA
Presymptomatic dx
screening for certain diseases before presenting with sxs
can be genetically tested before individual develops disease
-colon and breast cancer
may have earlier screening to minimize risk of developing disease
Testing for Drug Efficacy
number of genes are associated w/ sensitivity to specific therapeutic drugs
testing for gene variants guide drug treatment
-Abacavir - HIV tx can cause severe adverse rxns if pt has HLA-B variant
-psych meds
-warfarin
-HIV
-hep B/C
Incomplete penetrance
reveals presence or absence of disease-causing mutations but many genetic diseases
have incomplete penetrance
Chromatin
located in cells nucleus and contains chromosomes
Chromosomes
contain genes, basic units of inheritance
Genes
composed of DNA and histones that cause DNA to coil into tightly compressed structure
Genetic testing
helps to determine whether an individual carries specific disease-causing mutations
Carrier screening
identify heterozygous carriers for many recessive diseases
-CF
-Sickle cell
-Tacy-Sachs
helpful for reproductive decisions
-especially in populations where diseases are common
prevalence of some diseases have declined d/t increase in screening
If the carrier is positive (usually mom) then the
partner will undergo testing, even more complex testing
Amniocentesis
withdrawal of small amount of amniotic fluid from uterus @ 16 wks gestation
fetal cells within fluid cultured and karyotypes to detect chromosome abnormalities
low risk of fetal loss
What can be detected as an elevation of alpha fetoprotein level in amniotic fluid?
neural tube defects
spina bifida
anencephaly
Chorionic villus sampling (CVS)
extraving small amount of villous tissue (from placenta) from chorion @ 10-12 wks
doesn't require in vitro cell culturing for chromosome analysis
sufficient numbers directly available in tissue
higher fetal loss than amniocentesis
Preimplantation genetic diagnosis (PGD)
carried out on early embryos (8-12 cells) created by in vitro fertilization
1-2 cells removed from embryo (no damage) and cells tested for chromosome
abnormalities or single-gene disorders
, genetic disorder found=not implanted
Analysis of Fetal DNA in maternal circulation
6-8 wks gestation - fetal cells + cell-free fetal DNA can be found in mother's
bloodstream
-tested for disease-causing mutations
advantages: early dx and minimal risk to mother and fetus
rapidly cleared by renal system (16 hr 1/2 life)
Analytes
screening routine by measuring maternal serum samples
B-hCG + PAPP-A
+
nuchal translucency US
assess risk of conditions
-trisomies 21, 13, 18 + neural tube defects
does not evaluate DNA
Presymptomatic dx
screening for certain diseases before presenting with sxs
can be genetically tested before individual develops disease
-colon and breast cancer
may have earlier screening to minimize risk of developing disease
Testing for Drug Efficacy
number of genes are associated w/ sensitivity to specific therapeutic drugs
testing for gene variants guide drug treatment
-Abacavir - HIV tx can cause severe adverse rxns if pt has HLA-B variant
-psych meds
-warfarin
-HIV
-hep B/C
Incomplete penetrance
reveals presence or absence of disease-causing mutations but many genetic diseases
have incomplete penetrance
