Non-Mendelian Inheritance

Question 1

3 Laws of Mendelian Ineritance

Answer 1

• law of dominannce
• law of segregation
• law of independent assortment

Question 2

3 kinds of mendelian inheritance

Answer 2

automosal dominant, automosal recessive, X-linked

Question 3

What is non-mendelian inheritance

Answer 3

the inheritance of traits that have a more complex genetic basis than one gene with two alleles and complete dominance - several variants of several genes acting together

Question 4

Mechanisms of non-mendelian inheritance (give inheritance pattern and associated mechanism)

Learn as LO

Answer 4

• Incomplete Penetrance - environmental factor, genetic modifiers
• Genomic imprinting - variants from parents
• Extranuclear inheritance - e.g. mitochondria mutations
• Anticipation - e.g. triplet repeat expansion
• Complex - multi-genic risk

Question 5

Compare the environmental and genetic factors which contribute to human diseases

Answer 5

Environmental:
* Common
* Complex genetics
* Multi-factorial
* Low recurrence rate

Genetic:
* Rare
* Genetics simple
* Uni-factorial
* High recurrence rate

Question 6

what is penetrance

LO

Answer 6

The frequency with which a trait (/mutation) is manifested by individuals carrying the gene

Question 7

give examples of penetrance

probs don’t learn, just for understanding

Answer 7

CFTR - cystic fibrosis - 100%
BRCA1/2 - Breast cancer - 70-80%

Question 8

is mutation that causes cystic fibrosis (CFTR) autosomal recessive, dominant or X-linked

Answer 8

autosomal recessive

Question 9

what else can impact on cystic fibrosis as the CFTR mutation alone does not explain the severity of CF in organs and variation within families

Answer 9

• Genetic modifiers: genes that have small quantitative effects on the level of expression of another gene, may involve polymorphism
• Environmental factors: lifestyle, diet, infection, chemicals…

Question 10

what is genomic imprinting

Answer 10

• genes expressed from only 1 chromosome
• Parent-of-origin dependent

Question 11

epigenetic modifications

Answer 11

heritable changes in gene function not explained by changes in DNA sequences - DNA methylation?

Question 12

Give some genetic mechanisms of imprinting disorders

Answer 12

• Deletions
• Point mutations
• Imprinting errors
• Uniparental disomy (inheritance of chromosome pair from one parent)

Question 13

Uniparental disomy

Answer 13

occurs when a person receives two copies of a chromosome, or part of a chromosome, from one parent and no copies from the other parent. UPD can occur as a random event during the formation of egg or sperm cells or may happen in early fetal development

Question 14

uniparental diploidy - gyogenic

Answer 14

• 2 maternal genomes
• mass of embryo
• ovarian teratoma

Question 15

uniparental diploidy - androgenic

Answer 15

• 2 paternal genomes
• mass of placenta
• hydatidiform mole

Question 16

give 2 examples of imprinting disorders

Answer 16

• Angelman syndrome (epilepsy, mental retardation, inappropriate laughter)
• Prader-Willi Syndrome (PWS) (hypotonia, mental retardation, short stature, obesity)

Question 17

where is mitochondrial inheritance from

Answer 17

the mother

Question 18

what is a mutation hotspot

Answer 18

Mitochondria: lacks efficient DNA repair system and protective proteins (e.g. histones) - damaged by reactive oxygen species (e.g. free radicals)

Question 19

homoplasmy

Answer 19

cell whose copies of mitochondrial DNA are all identical

Question 20

heteroplasmy

Answer 20

presence of more than one type of organellar genome (e.g. mitochondrial DNA) within a cell

Question 21

where is disease more common in homoplasmy or heteroplasmy

Answer 21

heteroplasmy - high % mutation

Question 22

what does mitochondrial disease affect

Answer 22

tissues with high metabolic demand

Question 23

what is anticpation

Answer 23

A phenomenon in which the signs and symptoms of some genetic conditions tend to become more severe and/or appear at an earlier age as the disorder is passed from one generation to the next

Question 24

explain multigenic/complex inheritance

where seen, penetrance, what factor is significant to causing it

Answer 24

• often seen in common conditions (e.g. heart disease, breast cancer, autism)
• Multiple low penetrance variants - often extra-genetic affecting expression rather than DNA code
• Rare high penetrance variants in many genes causing same phenotype - schizophrenia
• Environmental factors often significant

Question 25

role of the environment in genetic disease

Answer 25

Environmental factors such as diet, temperature, oxygen levels, humidity, light cycles, and the presence of mutagens can all impact which genes are expressed, which ultimately affects phenotype