Functional Neurogenomics - 1

Question 1

Neurdevelopmental disorders

Answer 1

Disruption of events that lead to brain development
Inability to reach cognitive, emotional & motor developmental milestones
Heterogeneous = Multifactoral & polygenic
Mutations: Chr. rearrangement, CNVs, small indels, point mutations

Question 2

Rare genetic disorders

Answer 2

Alterations of single nucleotides
Overlap with neuropsychiatric disorders, but are genetically defined

Question 3

Neuropsychiatric disorders

Answer 3

Persistant, pervasive & pathological pattern of abnormal mood…

Question 4

Promise of genetics

Answer 4

Unbiased, causal, new disease mechanisms, target genes & therapeutics = personalized medicine

Question 5

Heritability

Answer 5

= Proportion of variation in a trait explained by inherited genetic variants
= How well differences in peoples genes account for differences in their traits

Question 6

Variation/Variance

Answer 6

How much a trait differs between people in a group
Heritability is a ratio of variance

Question 7

Genetic influences on variation

Answer 7

Additive: Sum of the effect of each allele at all loci which influence the phenotype
Non-additive: Interaction between alleles at the same locus (dominance) or at different loci (epistasis)

Question 8

Chromosomal linkage

Answer 8

Genes located physically close to each other on the same chromosome are more likely to be inherited as pair
Increased distance between two genes –> Increased probability of meiotic cross overs
Use genetic maps!

Question 9

Twin studies

Answer 9

Compare the rate of the trait sharing between MZ & DZ twins
MZ share all genetic variability, DZ share half their genetic variability

Question 10

Mendelian laws

Answer 10

1. Segregation: Each inherited trait is defined by a gene pair
2. Independent assortment: Inheritance of one trait is not dependent of another
3. Dominance: Express the allele form that is dominant

Question 11

Complex traits

Answer 11

Quantitative traits = Range of variation
Do not follow Mendelian inheritance laws
Many genes, that exert a small influence contributing to the disease, none by themselves can cause/explain the disease/trait

Question 12

Complex traits described by genetic architecture

Answer 12

Number of variants influencing a phenotype
Magnitude of their effect on the phenotype
Population frequency of these variants
Interactions with these variants with each other & environment

Question 13

Nature of Variants

Answer 13

Single Nucleotide Variant (SNV)
Coding variants
Non-coding variants
Indels
Short tandem repeats
Structural variant - Copy Number Variantion

Question 14

Frequency of variants

Answer 14

Common genetic variants - MAF >/=5%
Low-freuqency variants: MAF >/=1 but <5%
Rare genetic variants: MAF <1%

Question 15

Variant alleles

Answer 15

Matching human reference sequence or not
Being more frequent in population
Matching most recent common ancestor between human & chimpanze
Based on the disease association

Question 16

Catalogue common human variation

Answer 16

1.Sequence lots of individuals to discover variants
2. Catalogue common variants & haplotype blocks
3. Genotype much larger set of individuals
4. Estimate population specific properties

Question 17

Haplotypes

Answer 17

Specific set of alleles obeserved on a single chromosome
Arises because of recombination (more over time)

Question 18

Linkage disequilibirum

Answer 18

Non-random association between alleles at different loci
Loci in equilibrium segragate independently
Loci in disequilibirum segragte dependently = Linked
Depends on location = The closer together, the more in disequilibrium

Question 19

Epigenomics

Answer 19

Set of chemical modifications to DNA & histones in the cell –> Alter gene expression

Question 20

3D genome organization

Answer 20

Fractual globules: Polymer forms a globule made of smaller globules
Predicts that contact probability is a function of distance betweem two sides

Equilibrium globule: Polymer more attracted to itself –> Many knots
Collapses in globule to minimalize contact to surroundings