Lecture 9: Clinical Genetics Flashcards
What is a locus?
Position of a gene on a chromosome.
What is an allele?
A series of 2+ genes occupying same location of a chromosome.
What are the mendelian patterns of inheritance?
Autosomal dominant
Autosomal recessive
Sex-linked
What is XY and XX? What does it mean phenotypically? What is important about the Y?
X is inherently female.
Y is what gives male characteristics, so lack of Y = female.
XX is phenotypically female
XY is phenotypically male
Which sex chromosome is bigger?
X
Where do males get their X from?
Mother only
What is the key characteristic of an autosomal dominant disorder?
An affected person usually has at least one affected parent.
What are 2 examples an autosomal dominant disorder?
Huntington’s Disease: degenerative nerve disease from mutation in HTT gene
Marfan syndrome: degenerative connective tissue from mutation in FBN1 gene (prevents elastic fibers forming around connective tissue)
What is the key characteristic of an autosomal recessive disorder?
Males and females are equally affected.
What are 2 examples of an autosomal recessive disorder?
Cystic Fibrosis: mutation of CFTR, dysregulation of salts inc mucous
Sickle Cell: mutation of HBB gene, mutation in hemoglobin misshapen RBC
What are the key characteristic of an X-linked recessive disorder?
Usually affects males and all daughters of an affected male are carriers.
Females are affected only if father is affected and mother is at least a carrier.
What are 2 examples of X-linked recessive disorders?
color blindness, hemophilia
What are the key characteristics of an X-linked dominant disorder?
Very rare
Similar pedigree to autosomal dominant BUT no male to male transmission.
Note: This is because males can’t contribute an X. They only give a Y to a male.
What is an example of an X-linked dominant disorder?
rett syndrome: mutation in MECP2- early neurodevelopment disorder
What are the key characteristics of a Y-linked disorder?
ONLY MALE TO MALE
What is an example of a Y-linked disorder?
hypertrichosis
What are the key characteristics of a mitochondrial disorder?
Can affect both sexes, but only an affected mother can transmit it.
What is a disorder with mitochondrial DNA?
Leber’s Hereditary optic neuropathy: sudden vision loss around age 20, lack of mitochondria leads to cell death
(myopathy or neurological problems)
What is a polygenic trait?
A trait involving multiple alleles at different loci that affect a phenotype.
What is multifactorial inheritance?
Interaction between genes and environment.
What is penetrance for genetics?
% of individual with a given genotype that exhibit the phenotype.
What is nonpenetrance?
Failure of a phenotype to manifest even with a given genotype. (makes risk assessment hard since phenotype can skip a generation)
What is expressivity?
The extent to which a given genotype is expressed at the phenotypic level.
Note: You can have variable expressivity in the same family.
What causes expressivity?
Modifier genes
What is anticipation?
Specific type of variable expressivity caused by instability of triplet microsatellite repeat regions.
Note: With successive generations, age of onset decreases and severity worsens.
What is the difference between penetrance and expressivity?
Penetrance is whether a traits appears at all (either yes or no)
Expressivity is the degree to which a trait appears (sliding scale)
When do congenital disorders most commonly occur?
Embryonic period, which is weeks 3-8.
What are the four kinds of morphologic deficits?
Congenital malformations
Congenital deformations
Congenital disruptions
Congenital dysplasia
What is a congenital malformation?
Physical deficits due to INTRINSICALLY ABNORMAL DEVELOPMENT PROCESS
Example: Spina bifida, cleft lip/palate, neural tube defects
What is a congenital deformation?
Abnormal form or position of a body region caused by NON DISRUPTIVE MECHANICAL FORCE
Example: clubfoot, congenital hip defects
What is a congenital disruption?
A structural abnormality due to A DESTRUCTIVE FORCE
Example: Missing digits secondary to an amniotic band
What is a congenital dysplasia?
Abnormal growth or development of a tissue or organ
Example: Development dysplasia of the hip
What are teratogens?
Agents that can cause abnormalities during embryonic/fetal development.
What medication characteristics make them more likely to affect a fetus?
More lipophilic and low molecular weight drugs.
What is fetal alcohol syndrome? Characteristics?
Facial abnormalities: smooth philtrum, thin upper lip, small palpebral fissures
Growth deficit (< 10th percentile)
CNS abnormalities (small head, cognitive deficits, motor delays, attention deficits)
What are TORCH infections?
Toxoplasmosis
Other
Rubella
Cytomegalovirus (CMV)
Herpes
Other - varicella, listeriosis, leptospirosis, EBV, TB, Syphilis, HIV, parvovirus B19
What is congenital zika syndrome indicated by?
Severe microcephaly,
decreased brain tissue
retinal damage
limited ROM in joints
increased muscle tone
Note: Small brain, big muscles
What is the concern with ionizing radiation?
Pregnant people who get HEAVY doses.
What are the maternal metabolic diseases?
Diabetes
Folic acid deficiency
Hypothyroidism
What are some types of pre-conception screening?
Family history with pedigree
Carrier testing via DNA sequencing
Karyotype testing
What are some types of post-conception screening?
Ultrasound
Nuchal translucency
Cell-free DNA
Quad screening of AFP, hCG, inhibin A, unconjugated estradiol
What are some types of prenatal diagnostic testing?
Chorionic villus sampling after 10 weeks. (1 in 100 risk of miscarriage)
Amniocentesis after 15 weeks (1 in 200 risk of miscarriage)
Umbilical cord sampling after 16 weeks.
What 3 diseases are screened for in a newborn that are federally mandated?
Congenital hypothyroidism
Galactosemia
Phenylketonuria
What is the genetic information nondiscrimination act?
Prohibits health insurers from using genetic info to determine eligibility/premiums.
Also prohibits employers from discriminating using genetic info
What is a Barr body?
An inactivated X chromosome.
AKA females have 1, males have 0.
What is the SRY gene?
Gene found in the Y chromosome, initiates male sex development and anti-mullerian hormone production, which suppresses female gonads.
What can heavy doses of ionizing radiation cause?
Microcephaly, skeletal malformation, mental retardation
What is the purpose of a nuchal translucency test? When is it done?
11-13 weeks, results are combined with PAAP-A and hCG to check for trisomy risk.
What is the prupose of a cell-free DNA test? When is it done?
10-13 weeks, part of screening for trisomy.
What is the purpose of a quad-screen?
AFP, hCG, inhibin A, unconjugated estradiol
Screening for neural tube defects and down syndrome.
What is the purpose of a chorionic villus sampling?
DNA and chromosomal abnormality check.
What is the purpose of an amniocentesis?
Early, it is used to confirm an abnormal quad screen/US/carrier testing.
If done later, it is to check fetal lung development or infection.
What is the purpose of umbilical cord sampling?
Prenatal screening for disorders/infection.
