Mendelian and Non-Mendelian Inheritance- Lectures 43-44

Question 1

Describe autosomal dominance inheritance.

Answer 1

disease occurs in each succeeding generation
only one copy or allele of the gene bears the mutation, which is sufficient to cause disease in the family
males and females equally affected

Question 2

What is a gain of function mutation?

Answer 2

a mutation causing increased activity, a new activity, or a new pattern of gene expression

Question 3

What is a loss of function mutation?

Answer 3

a mutation causing decreased or lack of activity

Question 4

What is haploinsufficiency?

Answer 4

a single functional copy of a gene is insufficient for proper cell or tissue function or development

Question 5

Describe the dominant negative effect.

Answer 5

encoded mutant protein is part of a multiprotein complex that includes the wild-type protein and the presence of the mutant protein in the complex disrupts wild-type protein function

Question 6

Provide examples of autosomal dominate diseases.

Answer 6

Von Willebrand disease, pseudohypoparathyroidism, osteogenesis imperfecta, Marfan syndrome, neurofibromatosis, achondroplasia, polycystic kidney disease, Noonan syndrome, tuberous sclerosis, hypercholesterolemia, Huntington disease, hypertrophic cardiomyopathy

Question 7

What is autosomal recessive inheritance?

Answer 7

both copies of the gene must bear mutational changes for disease to manifest
carrier (heterozygous) parent transmit one mutant allele but does not express symptoms

Question 8

What are compound heterozygous mutations?

Answer 8

causes of autosomal recessive disease where different mutations on each allele are identified

Question 9

The _____ for most genetic diseases in the general population is very low.

Answer 9

carrier frequency

Question 10

Provide examples of autosomal recessive inherited disease.

Answer 10

cystic fibrosis, galactosemia, phenylketonuria, homocystinuria, congenital adrenal hyperplasia, alkaptonuria, spinal muscular atrophy, Freidrich ataxia, sickle cell anemia, thalassemias

Question 11

Describe X-linked inheritance.

Answer 11

males only have one x-chromosome so they are hemizygotes (have only one copy of X genes) where as females are have two and can be heterozygotes (can carry two different copies of an X-linked gene) or homozygotes (two of the same copies of the gene)

Question 12

What is X-linked dominate inheritance?

Answer 12

only one copy of the X-linked gene with a mutation is sufficient to cause disease
a female heterozygote is affected and a male hemizygote may be very severely affected or may not even survive (male lethal)

Question 13

What is X-linked recessive inheritance?

Answer 13

female heterozygotes may have little to no symptoms of the disease and male hemizygotes are the one who bear the classic manifestations of disease

Question 14

Describe X inactivation.

Answer 14

only one of the two X chromosome copies in cells of females is active in any given cell, the other copy is inactivated by an epigenetic mechanism involving the long non-coding RNA XIST –> may be apparent in those cells in which the wild type allele has been inactivated

Question 15

Provide examples of X-linked dominate conditions.

Answer 15

Lujan-Fryns syndrome, Rett syndrome, Fragile X syndrome

Question 16

Provide examples of X-linked recessive conditions.

Answer 16

hemophelia, muscular dystrophy, Fabry disease, retinitis pigmentosa, Hutnter syndrome, and adrenoleukodystrophy

Question 17

The association of a specific genetic variant with a characteristic pattern of physical characteristics is know as ______.

Answer 17

a genotype-phenotype correlation

Question 18

What factors affect genotype-phenotype correlations>?

Answer 18

X-inactiviation
penetrance
mosaicism
anticipation
variable expressivity
phenotypic heterogeneity
genetic or locus heterogeneity

Question 19

Describe mosaicism.

Answer 19

the state in which different populations of cells in a person or part of the body have different genetic makeups

Question 20

How does mosaicism occur?

Answer 20

spontaneous mutations arise after fertilization, limitign the change to one cell of many in the early embryo that is perpetuated through mitosis of mutated cell

Question 21

If a mutation occurs in non-gonadal cells, the change is called ____ and ____ be inherited.

Answer 21

somatic

cannot

Question 22

If a mutation occurs only in germline cells the individual has _____ and (will/will not) express symptoms that _____ be passed down to next generation.

Answer 22

gonadal mosaicism
will not
can

Question 23

Describe incomplete penetrance.

Answer 23

known mutations that do not always lead to disease due to a number of multigenic factors and modifiers or due to age/sex of patient

Question 24

Describe segmental mosaicism.

Answer 24

when the mutation occurs only in one type of cell in the body, resulting in disease that can be as mild and limited to only that segment of the body

Question 25

Describe anticipation.

Answer 25

further expansion of repeats (which occur primarily during meiosis in males) in succeeding generations, increasing disease severity manifesting at an earlier age of onset

Question 26

What is variable expressivity?

Answer 26

severity of the disease differs from person to person despite having the same genotype

Question 27

What causes variable expressivity?

Answer 27

various mulitgenic factors or environmental modifiers

Question 28

What is a pleiotropic mutation?

Answer 28

when a genotype produces diverse and differing organ system involvements

Question 29

Describe phenotypic heterogeneity.

Answer 29

variants within the same gene that may predispose to milder or more severe disease
different variants can result in seemingly distinct disorders

Question 30

What is genetic (locus) heterogeneity?

Answer 30

a single clinical phenotype arising from a mutation in multiple distinct genes

Question 31

The classic description of a mitochondrial inheritance pattern is one of ______.

Answer 31

maternal transmission

Question 32

Describe the hallmarks of maternal transmission of mitochondrial genes.

Answer 32

all affected females are transmitting the disease to all male and female offspring
none of the males are transmitting disease to either male or female offspring
however due to heteroplasmy, the threashold effect quantifies whether disease will be expressed in those cells

Question 33

Provide examples for mitochondrial inheritance.

Answer 33

myoclonic epilepsy with ragged red fibers (MERRF), Leber Hereditary optic neuropathy (LHON), Kearns-Sayer syndrome (KSS)

Question 34

What is epigenetics?

Answer 34

gene regulation that is a heritable pattern of gene function in the absence of any nucleotide sequence changes

Question 35

Provide examples of epigenetic mechanisms.

Answer 35

DNA methylation, histone modifications, and regulation by non-coding RNA

Question 36

What are the two epigenetic phenomena observed in humans?

Answer 36

imprinting

environmental epigenetic effects

Question 37

Describe imprinting.

Answer 37

act of suppressing gene expression, not allowing for biallelic expression of the gene but preferentially allowing for only mono-allelic expression
depends on parent of origin
mediated by DNA methylation and histone modification under control of imprinting centers

Question 38

Describe the pathway of maternally inherited imprinting.

Answer 38

Adult somatic cells will carry maternally inherited imprinted cells in both sexes
during creation of the germline, imprinting is “erased”
once gametes are created, the genes in each gamete are imprinted in accordance with their sex (both egg cells will contain only imprinted copies of the gene whereas both sperm cells will contain the gene in its non-imprinted form)

Question 39

Describe the pathway of paternally inherited imprinting.

Answer 39

Adult somatic cells will carry paternally inherited imprinted cells in both sexes
during creation of the germline, imprinting is “erased”
once gametes are created, the genes in each gamete are imprinted in accordance with their sex (both egg cells will contain only un-imprinted copies of the gene whereas both sperm cells will contain the gene in its imprinted form)

Question 40

Describe the possible causes of Prader-Wili syndrome.

Answer 40

Maternally imprinted gene
mutation in the paternal copy will result in no active copy producing phenotype
uniparental disomy where both copies of the gene come from the mother would result in no active copies of the gene

Question 41

Describe the possible causes of Angelman syndrome.

Answer 41

Paternally imprinted gene
mutation in the maternal copy will result in no active copy producing phenotype
uniparental disomy where both copies of the gene come from the father would result in no active copies of the gene

Question 42

What is the most common mechanism of uniparental disomy (UPD)?

Answer 42

trisomy rescue

Question 43

Provide examples of environmental factors that can contribute to epigenetic changes.

Answer 43

environmental exposures (toxins/chemicals)
stressors (child abuse, fasting/starvation, jobs)
well-being (diet, exercise, meditation)