Genetics

Question 1

The concordance of autism in monozygotic twins is _____ times that for dizygotic twins

Answer 1

8

Question 2

What developmental regressive disorder is X-linked and LETHAL (hemizygous MECP2 variant) in males (thus, you only see live, females affected by it)?

Answer 2

Rett Syndrome

Question 3

Diagnostic approach to autism

Answer 3

Family Hx
Physical exam (dysmorphic features)
Genetic testing (chromosomes, sequences, etc.)
Brain MRI (if indicated, like microcephaly and seizures)

Question 4

Copy number variant most common in those with Schizophrenia (hint: same for DiGeorge syndrome)

Answer 4

22q11

Question 5

A genetic approach to find relatively-common variants for various diseases; NOT diagnostic, just shows association and they might be co-inherited by proximity

Answer 5

Genome Wide Association Study (GWAS)

Question 6

Heritable cellular and physiologic traits (e.g. gene expression) that are NOT due to genetic sequence variations (“heritable” at the cellular level, not at the organismal level); examples are methylation, histone modifications, non-coding RNAs and environmental exposures (chemicals, drugs, etc.)

Answer 6

Epigenetics

Question 7

Method of Epigenetics; covalant modification of cytosine residues of nucleotides, important for chromosome stability and transcriptional “silencing”; example is X-chromosome inactivation

Answer 7

DNA methylation (red dots)

Question 8

(Methylated/Unmethylated) cytosines are associated with genes being switched on

Answer 8

Unmethylated (white dots indicate lack of methylation)

Question 9

(Acetylated/Deacetylated) histones are associated with genes being switched off

Answer 9

Deacetylated (HDAC)

Question 10

What makes a gene accessible and active (in regards to methylation and histones)

Answer 10

Unmethylated
Acetylated histones (upper) (white dots mean lack of methylation)

Question 11

Role of MECP2 in Rett Syndrome

Answer 11

Normally MECP2 Encodes Methyl CpG binding protein–> binds methylated DNA and recruits/activates transcription factors.

(A mutation of MECP2 causes Rett Syndrome; female has one mutation copy and one normal copy; the male is lethal).

Question 12

Rare complication of pregnancy characterized by the abnormal growth of chorionic villi; mass of fetal tissue resembling a “bunch of grapes”; “complete” is ENTIRELY paternal origin either by a empty ovum has a single sperm endoreplicate (90%) or fertilzed by 2 sperm (10%)

Answer 12

Molar pregnancy

Question 13

Epigenetic phenomenon through which the expression of certain genes is regulated in a manner specific to the parent of origin

Answer 13

Genomic Imprinting

Question 14

Inheritance of both copies of a chromosome from the SAME parent without contribution from the other parent; may “unmask” recessive conditions if isodisomy (two copies of same chromosome from same parent)

Answer 14

Uniparental Disomy (UPD)

Question 15

Rare genetic disorder due to genetic deletions; results in hypotonia and poor feeding at birth with a constant sense of hunger (hyperphagia). Overweight, insatiable appetite, and poor linear growth from childhood on; may have hypogonadism; can GREATLY treat with GH replacement (improves lean muscle mass)

Answer 15

Prader-Willi Syndrome

Question 16

Rare genetic disorder due to either de novo deletions or defect in UBE3A (ubiquitin-protein ligase); causes developmental disabilities and neurological problems (speech impairment, seizures, microcephaly, etc.); often smile and laugh frequently, and have happy, excitable personalities

Answer 16

Angelman Syndrome

Question 17

Familial Angelman syndrome results only when a pathogenic UBE3A is inherited on the paternal/maternal allele.

Answer 17

maternal!!

Question 18

Condition that is classified as an overgrowth syndrome due to hypomethylation of DMR2; affected infants are considerably larger than normal (macrosomia), tend to be taller than their peers and have enlarged body parts (macroglossia, visceromegaly, etc.); also more prone to embryonal tumors (Wilms, hepatoblastoma, etc.)

Answer 18

Beckwith-Wiedeman Syndrome