Genetic inheritance Base Principles

Question 1

Diploid mammal inherits DNA from

Answer 1

male and female parents
Female:
1 copy of each autosomal chromosome
X sex chromosome
Mitochondrial genome

Male:
1 copy of each autosomal chromsome
X or Y sex chromosome

Question 2

matrilineal inheritance

Answer 2

inheritance of trait or gene directly from mother (mitochondrial DNA)

Question 3

patralineal inheritance

Answer 3

inheritance of trait or gene directly from father (y choromosome)

Question 4

relative size of genome compoenents

Answer 4

Largest autosomal -> X -> Y -> mitochondrial

Question 5

modes of inheritance

Answer 5

simple or complex

Question 6

simple inheritance pattern

Answer 6

phenotypic outcome is result of single gene (Mendilian; monogenic traits= mendilian); many genetic dx in companion animals fall under this umbrella ex. blood type, cat coat color ect

Question 7

complex inheritance pattern

Answer 7

“complex trait”/ polygenic; multiple genes and environmental factors all contribute to make trait value; most traits = complex; often qualitative traits measured on continuum not binary yes/ no

Question 8

Nuclear genome

Answer 8

• autosomal and sex chromsomes
• 3.4 billion bases
• ~20k genes
• inherited from both parents
• extensive recombination
• large # variable regions useful for studying diversity

Question 9

Mitochondrial genome

Answer 9

• circular double stranded
• 16.5kb bases
• 35 genes
• Maternal inheritance
• No recombination
• Useful for studying lineage

Question 10

consequences of X vs Y genome size

Answer 10

X is larger than Y so females get same genomic inheritance from both parents males get more nucleic acids from mom than from dad

Question 11

most clinically significant phenotypes we see are

Answer 11

homozygous receissive

Question 12

most autosomal dominant disorders

Answer 12

more severe in homozygotes than heterozygotes

Question 13

mammals are diploid so

Answer 13

two alleles at most loci

Question 14

Two main factors controlling simple (single gene) inheritance pedigree patterns

Answer 14

1. Chromsomal location of gene (autosomal, X linked (or other) ); male mammals are hemizygous for X
2. phenotype expression pattern for allele of interest (dominant or recessive)

Question 15

Most typical simple modes of inheritance

Answer 15

• Autosomal dominant
• Autosomal recessive
• X-linked dominant
• X- linked recessive

Question 16

Blood types

Answer 16

O, B,A; come from O being recessive building block antigen A and B have additional sugar decorating them; A and B are codominat with each other and both A and B are dominant to O

Question 17

A phenotype

Answer 17

AA or AO both lead to A oligosacharides on cell surface (AA A only AO A and O on cell surface) but in both cases they are immuno-reactively equivalent (phenotype is just A) works same in case of B

Question 18

AB phenotype

Answer 18

express both A oligosacharides and B oligosaccharides on cell surface so both are immune-reactive so they are co dominant

Question 19

A B and O forms genetic differences

Answer 19

• O single bp deletion
• A and B have 7 SNP changes between them resulting in AA changes that shift substrate specificity
• 5’ UTR minisatalite repeats
• other SNPs in non-coding and 3’ UTR regions

Question 20

P (A or B)=

Answer 20

P(A)+P(B)= 100%

so long as events A and B are mutually exclusive (only one can occur at a time)

Question 21

many recessive disorders are

Answer 21

enzyme defects where proper fx of single normal allele can prevent clinical problems

Question 22

Dominant disorders can result from

Answer 22

haploinsufficency, dominant negative effect, and gain of function

Question 23

haploinsufficency

Answer 23

single normal allele is not sufficient to produce normal phenotype

Question 24

dominant negative effect

Answer 24

altered gene product antagonizes normal product

Question 25

gain of function

Answer 25

changing the gene product's specificity or expression pattern rather than reducing or eliminating it (ex oncogene Ras confers a dominant predisposition to cancer)

Question 26

P (A and B)=

Answer 26

P (A) x P(B) | outcome of A does not effect outcome of B (they are independent)

Question 27

Pedigree analysis

Answer 27

``` Male= box Female= circle diseased= filled in undiseased= unfilled deceased= line through ```

Question 28

Autosomal dominant inheritance

Answer 28

- dx not obscured in pedigrees; every affected animal has affected parent (also true for x linked dominant disorders) - 1 copy of mutation = sufficient to cause dx - male to male dx transmission possible (not true in X linked dominant traits) - Homozygotes (DD) may be rare as dx and are often more severe than heterozygotes (Dd)

Question 29

Autosomal recessive inheritance

Answer 29

- Dx alleles are obscured in pedigrees, affected animals may or may not have affected parents - two copies of mutation needed to cause dx so its only in homozygotes - affected animals get one mutant allele from each parent - parents can inherit allele from same source bc inbreeding (v common in domestic animal breeding)

Question 30

chances of a phenotypically normal offspring of two heterozygous parents for autosomal recessive being carrier

Answer 30

2/3 (bc 1/4 RR, and 2/4 Rr 1/4 rr= negated because phenotypically normal so instead goes to 1/3 RR and 2/3 Rr)

Question 31

X linked inheritance

Answer 31

- Males hemizygous for X linked traits (genotypes can be AY or aY) - Males will show trait whether allele is dominant or recessive - Females can be homozygous or heterozygous

Question 32

X inactivation

Answer 32

in female somatic cells random X-inactivation means only 1 x will be transcriptionally active (can be maternal or paternal); cells depending from this cell will have same inactive X; can -> skewed distribution of cells with active X bearing dx allele -> disease

Question 33

X linked dominant inheritance

Answer 33

- dx not obscured on pedigrees (typically every effected animal has effected parent) - male male transmission NOT possible - All female offspring of affected male will be affected - pattern of transmission through females in equivalent to autosomal dominant inheritance; X linked dominant traits more frequently observed in females although heterozygous females usually more mildly affected than hemizygous males

Question 34

1/3000 male cats is calico

Answer 34

kleinfelters syndrome (xxy)

Question 35

X linked recessive inheritence

Answer 35

- trait seen more frequently in males than females - male to male transmission does not occur - female offspring of effected males are obligate carriers - affected females are homozygous

Question 36

monogenic disorders

Answer 36

dictated by single gene

Question 37

polygenic disorders

Answer 37

dictated by multiple genes

Question 38

can you have insufficient information from pedigree analysis to determine mode of inheritance

Answer 38

yes in which case write that there is insufficient info