Principles of Genetic Inheritance

Question 1

Lyonization (X-inactivation)

Answer 1

When one of a females X chromosomes become inactivated.

Question 2

Mosiacism

Answer 2

Being composed of 2 cells that have different genotypes (and karyotypes).

Question 3

Meiosis creates genetic diversity in 2 ways:

Answer 3

1. Random segregation of homologues.

2. Crossing-over.

Question 4

Meiotic errors (2)

Answer 4

1. Polyploidy: presence of more than 2 complete sets of chromosomes.
2. Aneuploidy: cells missing chromosomes or with an additional individual chromosome.

Question 5

Turner Syndrome

Answer 5

45, XO karyotype.
Female without a Y. Causes ovarian hypofunction/premature ovarian failure. Unlikely to undergo puberty without hormone therapy. Most are infertile. Normal intelligence.

Question 6

Klinefelter Syndrome

Answer 6

47, XXY. Can have variability in X numbers, which will increase symptoms.
Male. Some can have mild symptoms/none. Varying degrees of cognitive, social, behavioral or learning difficulties. Low T and small testes.

Question 7

47, XX +21 Downs Syndrome

Answer 7

Most common. Increased risk with maternal age.

Question 8

47, XX +13 Patau Syndrome

Answer 8

Severe developmental abnormalities. Most die within 1 week.

Question 9

47, XX +18 Edwards Syndrome

Answer 9

Abnormal development. Most die within 1 year.

Question 10

Genomic Imprinting

Answer 10

When, for some reason, one of the alleles is transcriptionally inactive. It is basically gene silencing, via methylation of the 5’ region of the gene. During meiosis, imprints are erased and new ones are set.

Question 11

Prader-Willi Syndrome

Answer 11

Deletion of region of chromosome 15 on paternal chromosome. Short stature, small hands/feet, obesity, intellectual disability.

Question 12

Angelman Syndrome

Answer 12

Deletion of region of chromosome 15 on maternal chromosome. Severe intellectual disability, seizures, ataxic gait.

Question 13

Uniparental Disomy

Answer 13

2 chromosomes inherited from the same parent (will have parent specific imprinting).

Question 14

Pleiotropy

Answer 14

Same genotype but multiple phenotypes.

Question 15

Penetrance

Answer 15

Frequency that a gene manifests itself (i.e. how many people with that genotype express that phenotype?)

Question 16

Variable Exressivity

Answer 16

Describes the range of phenotypes between individuals with the same genotype.

Question 17

Locus Heterogeneity

Answer 17

Trait caused by mutations i genes at different chromosomal loci.

Question 18

Mitochondrial DNA (mtDNA)

Answer 18

Encodes rRNA, tRNA, and proteins involved in oxphos. Transcription takes place inside of the nucleus. Does not contain introns. Inherited exclusively from the mother and has a 10x higher mutation rate. than nDNA, due to lack of DNA repair mechanisms and priximity to oxphos system (free rads).

Question 19

LHON

Answer 19

Mito d/o.

Degenerates retinal ganglion cells. Causes acute or subacute loss of central vision by teens or 20s.

Question 20

MELAS

Answer 20

Mito d/o.
Affects mostly brain, NS and muscles.
Causes stroke, dementia and lactic acidosis.

Question 21

Liability Distribution (Multifactoral Inheritance)

Answer 21

Occurs in disease that do not follow the bell-curve distribution.

Question 22

Threshold of Liability (Multifactoral Inheritance)

Answer 22

Must be crossed before the disease is expressed. (slide 64).