Lecture 4 Clinical Genetics

Question 1

What is a locus?

Answer 1

Position of a gene on a chromosome.

Question 2

What is an allele?

Answer 2

A series of 2+ genes occupying same location of a chromosome.

Question 3

What are the mendelian patterns of inheritance?

Answer 3

Autosomal dominant
Autosomal recessive
Sex-linked

Question 4

What is XY and XX? What does it mean phenotypically? What is important about the Y?

Answer 4

X is inherently female.
Y is what gives male characteristics, so lack of Y = female.

XX is phenotypically female
XY is phenotypically male

Question 5

Which sex chromosome is bigger?

Answer 5

X

Question 6

Where do males get their X from?

Answer 6

Mother only

Question 7

What is the key characteristic of an autosomal dominant disorder?

Answer 7

An affected person usually has at least one affected parent.

Question 8

What is the key characteristic of an autosomal recessive disorder?

Answer 8

Males and females are equally affected.

Question 9

What are the key characteristic of an X-linked recessive disorder?

Answer 9

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.

Question 10

What are the key characteristics of an X-linked dominant disorder?

Answer 10

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.

Question 11

What are the key characteristics of a Y-linked disorder?

Answer 11

ONLY MALE TO MALE

Question 12

What are the key characteristics of a mitochondrial disorder?

Answer 12

Can affect both sexes, but only a mother can transmit it.

Question 13

What is a polygenic trait?

Answer 13

A trait involving multiple alleles at different loci that affect a phenotype.

Question 14

What is multifactorial inheritance?

Answer 14

Interaction between genes and environment.

Question 15

What is penetrance for genetics?

Answer 15

% of individual with a given genotype that exhibit the phenotype.

Question 16

What is nonpenetrance?

Answer 16

Failure of a phenotype to manifest even with a given genotype. (makes risk assessment hard since phenotype can skip a generation)

Question 17

What is expressivity?

Answer 17

The extent to which a given genotype is expressed at the phenotypic level.

Note: You can have variable expressivity in the same family.

Question 18

What causes expressivity?

Answer 18

Modifier genes

Question 19

What is anticipation?

Answer 19

Specific type of variable expressivity caused by instability of triplet microsatellite repeat regions.

Note: With successive generations, age of onset decreases and severity worsens.

Question 20

What is the difference between penetrance and expressivity?

Answer 20

Penetrance is whether a traits appears at all (either yes or no)

Expressivity is the degree to which a trait appears (sliding scale)

Question 21

When do congenital disorders most commonly occur?

Answer 21

Embryonic period, which is weeks 3-8.- highest vulnerability

Question 22

What are the four kinds of morphologic deficits?

Answer 22

Congenital malformations
Congenital deformations
Congenital disruptions
Congenital dysplasia

Question 23

What is a congenital malformation?

Answer 23

Physical deficits due to INTRINSICALLY ABNORMAL DEVELOPMENT PROCESS

Example: Spina bifida, cleft lip/palate, neural tube defects

Question 24

What is a congenital deformation?

Answer 24

Abnormal form or position of a body region caused by NON DISRUPTIVE MECHANICAL FORCE

Example: clubfoot, congenital hip defects

Question 25

What is a congenital disruption?

Answer 25

A structural abnormality due to A DESTRUCTIVE FORCE Example: Missing digits secondary to an amniotic band

Question 26

What is a congenital dysplasia?

Answer 26

Abnormal growth or development of a tissue or organ Example: Development dysplasia of the hip

Question 27

What are teratogens?

Answer 27

Agents that can cause abnormalities during embryonic/fetal development.

Question 28

What medication characteristics make them more likely to affect a fetus?

Answer 28

More lipophilic and low molecular weight drugs.

Question 29

What is fetal alcohol syndrome? Characteristics?

Answer 29

Facial abnormalities: smooth philtrum, thin upper lip, small palpebral fissures Growth deficit (< 10th percentile) CNS abnormalities (small head, cognitive deficits, motor delays, attention deficits)

Question 30

What are TORCH infections?

Answer 30

Toxoplasmosis Other Rubella Cytomegalovirus (CMV) Herpes Other - varicella, listeriosis, leptospirosis, EBV, TB, Syphilis, HIV, parvovirus B19

Question 31

What is congenital zika syndrome indicated by?

Answer 31

Severe microcephaly, decreased brain tissue retinal damage limited ROM in joints increased muscle tone Note: Small brain, big muscles

Question 32

What is the concern with ionizing radiation?

Answer 32

Pregnant people who get HEAVY doses.

Question 33

What are the maternal metabolic diseases?

Answer 33

Diabetes Folic acid deficiency Hypothyroidism

Question 34

What are some types of pre-conception screening?

Answer 34

Family history with pedigree Carrier testing via DNA sequencing Karyotype testing

Question 35

What are some types of post-conception screening?

Answer 35

US Nuchal translucency Cell-free DNA Quad screening of AFP, hCG, inhibin A, unconjugated estradiol

Question 36

What are some types of prenatal diagnostic testing?

Answer 36

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.

Question 37

What 3 diseases are screened for in a newborn that are federally mandated?

Answer 37

Congenital hypothyroidism Galactosemia Phenylketonuria

Question 38

What is the genetic information nondiscrimination act?

Answer 38

Prohibits health insurers from using genetic info to determine eligibility/premiums. Also prohibits employers from discriminating using genetic info

Question 39

What is a Barr body?

Answer 39

An inactivated X chromosome. AKA females have 1, males have 0.

Question 40

What is the SRY gene?

Answer 40

Gene found in the Y chromosome, initiates male sex development and anti-mullerian hormone production, which suppresses female gonads.

Question 41

What can heavy doses of ionizing radiation cause?

Answer 41

Microcephaly, skeletal malformation, mental retardation

Question 42

What is the purpose of a nuchal translucency test? When is it done?

Answer 42

11-13 weeks, results are combined with PAAP-A and hCG to check for trisomy risk.

Question 43

What is the prupose of a cell-free DNA test? When is it done?

Answer 43

10-13 weeks, part of screening for trisomy.

Question 44

What is the purpose of a quad-screen?

Answer 44

AFP, hCG, inhibin A, unconjugated estradiol Screening for neural tube defects and down syndrome.

Question 45

What is the purpose of a chorionic villus sampling?

Answer 45

DNA and chromosomal abnormality check.

Question 46

What is the purpose of an amniocentesis?

Answer 46

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.

Question 47

What is the purpose of umbilical cord sampling?

Answer 47

Prenatal screening for disorders/infection.