Genetics Flashcards
3 sources you can use for genetic testing
Blood draw, cheek swab, saliva sample
All are equally accurate however blood draw gets more DNA whereas saliva/cheek samples may have more fails
The average individual has __ pairs of chromosomes and __ chromosomes total
23, 46
The human body has roughly _______ genes
30,000
Describe metaphase
stage during cell division in which the nucleus dissolves, chromosomes condense and move together aligning in the center of the dividing cell
Describe a karyotype
Image of chromosomes from a microscope are lined up and numbered 1-22 plus sex chromosomes
In Autosomal Dominant Inheritance each offspring has a ___ chance of being affected, and a ___ chance of being unaffected
50%, 50%
T/F male to male transmission can occur in autosomal dominant inheritance
True
Are males or females more likely to be affected in autosomal dominant inheritance?
Males and females are equally likely to be affected
If parents are both carriers of a recessive gene mutation what are the chances of inheriting both normal genes, being a carrier, and being affected (inheriting both mutations)?
25% chance of both normal genes
50% chance of being a carrier
25% chance of being affected
If one parent is a carrier of a recessive gene what are the possible outcomes for the children?
50% unaffected, 50% carriers
If one parent is affected by a recessive gene what is the outcome for the children?
all will be carriers
What type of inheritance is never transmitted directly from father to son, has a much higher incidence of the condition in males than in females?
X- linked Recessive inheritance
What nucleotides are Pyrimidines? Purines?
Pyrimidines = Cytosine, Thymine
Purines = Guanine, Adenine
What type of genetic mutation is most common?
loss of function
BRCA1, BRCA2 (as well as most cancer genes), and cystic fibrosis (CFTR) are examples of _____ of function mutations
Loss
Fragile X syndrome (FMR1) and FGFR3 gene (achondroplasia and craniosynostosis) are examples of ___ of function mutations
gain
Loss of function mutations in what genes causes increased cell proliferation and tumor development?
BRCA1, BRCA2 - tumor suppressor genes
Are BRCA1, and BRCA2 autosomal recessive or autosomal dominant?
Autosomal dominant
What does loss of function in the CFTR gene cause?
Cystic Fibrosis, loss of function in protein required for chloride transport channels results in abnormal build up of mucus in various organs, obstructive lung disease, pancreatic insufficiency, GI problems, infertility - congenital bilateral absence of vas deferens (CBAVD) in males
Cystic fibrosis is autosomal recessive or autosomal dominant?
Autosomal recessive
FMR1 disorders are __ linked disorders, name 3
X linked
Fragile X syndrome (FXS)
Fragile X associated tremor/ataxia (FXTAS)
Fragile X associated primary ovarian insufficiency (FXPOI)
More than ___ CGG repeats indicates trinucleotide repeat expansion disorder/FMR1 disorder
45
Characteristic of fragile X syndrome are-
> 200 CGG repeats
usually in males (1 X chromosome)
Symptoms of fragile X syndrome
Developmental delay, intellectual disability, ASD 50-70%, hypotonia, strabismus, seizures, sleep disorders, characteristic facial features
2 conditions that are a result of an FMR1 premutation
Fragile X-associated tremor/ataxia syndrome (FXTAS)
Fragile X-associated primary ovarian insufficiency (FXPOI)
In fragile X associated tremor/ataxia and primary ovarian sufficiency syndromes what causes health concerns?
55-200 CGG repeats = too much mRNA production, toxicity causes health concerns
Disorder that causes progressive cerebellar ataxia, intention tremor, cognitive impairment, and psychiatric disorders, males and females both affected
Fragile X associated tremor/ataxia syndrome (FXTAS)
Disorder that affects only women, diminished ovarian reserve and infertility
Fragile X-associated primary ovarian insufficiency (FXPOI)
Describe Achondroplasia
FGFR3 mutation, average sized trunk, short arms and legs, cartilage is not correctly converted to bone, normal lifespan and intelligence
Achondroplasia is autosomal dominant or autosomal recessive?
Autosomal dominant, 80% of cases are de novo (new genetic mutation occurring at the time of conception that is now inheritable)
What is caused by a gain of function mutation in FGFR3 that results in continuous signals to slow bone growth?
Achondroplasia
Examples of microdeletion syndromes
Angelman syndrome, pader-willi syndrome, digeorge syndrome, wolf-hirschhorn syndrome, cri-du-chat syndrome
___% of DiGeorge syndrome is inherited, the rest is de novo
10%, most cases are de novo
Digeorge syndrome is caused by deletion of ___ genes on chromosome 22 at location q11.2
30-40 genes usually
Problems associated with DiGeorge syndrome? What is Digeorge syndrome also called?
AKA 22q11.2 deletion syndrome
Cardiac abnormalities, recurrent infections, distinctive facial features, cleft/high ached palate, low calcium->seizures, developmental delay and intellectual disability
What are indications for karyotyping?
Aneuploidy (trisomy, monosomy), recurrent miscarriages, can detect translocations
What is Trisomy 21 and what are the symptoms
Down syndrome - intellectual disability, distinct facial features, hypotonia, congenital heart defect in 50%, celiac disease, hypothyroidism, hearing and vision concerns
People with down syndrome have increased risk for what two diseases?
Leukemia and alzheimers
What is trisomy 18 and what are the symtoms
Edwards Syndrome - intrauterine growth restriction (IUGR), low birth weight, congenital anomalies and birth defects, intellectual disability
Only 5-10% of babies with ______ __ live past their first year
Trisomy 18 (Edwards syndrome), and Trisomy 13 (Patau syndrome)
What is Trisomy 13 and what are the symptoms
Patau syndrome - heart defects, brain/spinal cord anomalies, small/poorly developed eyes, polydactyly, cleft lip and/or palate, hypotonia
_____ _________ aneuploidy is less severe than other aneuploidies and results in fertility and hormone concerns
Sex chromosome aneuploidy
What is Monosomy X also known as?
turner syndrome, females who only have one x chromosome
Symptoms of Monosomy X
Turner Syndrome - affects females only, short stature, premature ovarian insufficiency, infertility, webbed neck, low hairline, lymphedema, normal intelligence
What congenital heart defect is seen in Monosomy X?
coarctation of the aorta
Trisomy X is also called ____ __ syndrome and affects ____ only
Triple X syndrome, females
What are symptoms of Trisomy X
Few symptoms, may be taller than average, 10% have seizures or kidney anomalies, normal fertility, intelligence, and appearance
What sex chromosomes do men with Klinefelter syndrome have?
XXY
What are symptoms of Klinefelter syndrome
affects males only, taller than average, infertility, small testes, reduced testosterone, gynecomastia, decreased muscle mass, 10% with ASD
Up to ___% of men with Klinefelter syndrome are never diagnosed
75%
What sex chromosomes does someone with Jacobs syndrome have?
XYY
What are symptoms of Jacobs syndrome?
Taller than average, increased risk for delayed speech and language skills, learning disabilities, delayed motor skills, hypotonia, normal sexual development and fertility
What is Fluorescence in situ hybridization (FISH) used for?
to identify presence of a chromosome (aneuploidies) or specific sections of a chromosome (large deletions/duplications), rarely used, have to know exactly what you are looking for
What is chromosomal microarray (CMA) used for?
Detects imbalances of chromosomal material due to deletions or duplications, measure of genetic material
What are indications for a Chromosomal microarray (CMA)?
Developmental delay, intellectual disability, ASD, multiple congenital anomalies, syndromes related to known deletion/duplication
*Usually first line testing
When is single gene testing used?
To rule in or rule out a specific disorder caused by a single gene
What diseases is single gene testing typically used for?
Cystic fibrosis, Huntingtons, BRCA1/BRCA2, Marfans
Marfans syndrome is autosomal ______ and ____% of cases are de novo
dominant, 25%
What are symptoms of marfans syndrome?
Connective tissue disorder - vision problems due to dislocations of the lens, problems with the aorta (aortic dissection), mitral valve prolapse, scoliosis, kyphosis, pectus excavatum/carinatum, narrow face and crowded teeth
What are some examples of conditions that require multiple gene testing?
Polycystic kidney disease
Cardiomyopathy
Early onset Alzheimer’s
inherited cancers
When is whole exome sequencing (WES) indicated?
After normal CMA or multi-gene panel when there is developmental delay, intellectual disability, ASD, or multiple congenital anomalies
What is the difference between whole exome sequencing (WES) and whole genome sequencing (WGS) and when is WGS indicated?
WGS is a full DNA analysis including coding and noncoding regions and can detect single nucleotide variants, insertions, and deletions.
WES just sequences coding regions and may not include deletions and duplications.
WGS is indicated after normal WES or multigene panel in patients severely affected or with multiple anomalies.
Define informative negative
True negative, able to rule something out with extreme confidence such as known familial mutation or specific condition
Define uninformative negative
No mutation was identified but still cannot determine the cause of the condition or whatever led the patient to testing
What happens when a variant of uncertain significance (VUS) is found?
Innocent until proven guilty, Medical management does not change based on this result, lab continues to study finding and typically is reclassified as normal (95%)
T/F family members should also be tested for VUSs?
False, family members should not be tested unless the lab indicates otherwise, 95% reclassified as normal variants
What is the difference between diagnostic and predictive testing?
Diagnostic is used to confirm a suspected diagnosis based on signs and symptoms. May assist in treatment.
Predictive is used to detect mutations that may appear later in life when patients currently have no symptoms. May assist in family planning.
_______ screening is used for family planning for recessive conditions such as cystic fibrosis.
Carrier
Newborn screening varies by state but all states currently test for _________ and __________
PKU and congenital hypothyroidism
What are some noninvasive prenatal tests (NIPT)?
- Cell free DNA - mom has babys DNA in her blood, blood draw around 8-12 weeks
- Testing chromosomes 13, 18, 21, X, and Y for extra or missing copies
- Some microdeletions (not recommended due to low accuracy, if positive have to do amniocentesis)
________ is the most accurate test that can be performed during pregnancy to diagnose certain genetic disorders, birth defects, and other conditions.
Amniocentesis
When are amniocentesis typically performed?
between 15-20 weeks
What are indications for an amniocentesis? (5)
- Age 35+
- prenatal screening (NIPT) shows baby may have a problem
- You or your partner have a family Hx of genetic disorder/neural tube defect
- genetic testing showed you carry a genetic disorder
- you or your partner already have a child with a genetic disorder or birth defect
Difference between chorionic villus sampling (CVS) and amniocentesis?
CVS samples the placenta which is genetically identical to the fetus, does not enter the amniotic sac to collect amniotic fluid like you would in an amniocentesis
Pros/cons to chorionic villus sampling (CVS)?
Pro - can be performed earlier in pregnancy 10-13 weeks
Cons - cannot diagnose neural tube defects, which amniocentesis can
(Both have risks so avoid if you can but doing the amniocentesis to begin with is better than doing the CVS then having to still do the amniocentesis)
_____________ ________ __________ is a test only used in IVF to determine if an embryo is affected with a genetic mutation or chromosome abnormality, it is very limited and you must know what you’re looking for.
Preimplantation Genetic Testing (PGT)
Types of PGT (3)
PGT-A (aneuploidy)
PGT-M (monogenic) - known genetic mutation/inherited disease
PGT-SR (structural rearrangement) - chromosome abnormalities/translocations
