Genetic inheritance Base Principles Flashcards
Diploid mammal inherits DNA from
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
matrilineal inheritance
inheritance of trait or gene directly from mother (mitochondrial DNA)
patralineal inheritance
inheritance of trait or gene directly from father (y choromosome)
relative size of genome compoenents
Largest autosomal -> X -> Y -> mitochondrial
modes of inheritance
simple or complex
simple inheritance pattern
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
complex inheritance pattern
“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
Nuclear genome
- autosomal and sex chromsomes
- 3.4 billion bases
- ~20k genes
- inherited from both parents
- extensive recombination
- large # variable regions useful for studying diversity
Mitochondrial genome
- circular double stranded
- 16.5kb bases
- 35 genes
- Maternal inheritance
- No recombination
- Useful for studying lineage
consequences of X vs Y genome size
X is larger than Y so females get same genomic inheritance from both parents males get more nucleic acids from mom than from dad
most clinically significant phenotypes we see are
homozygous receissive
most autosomal dominant disorders
more severe in homozygotes than heterozygotes
mammals are diploid so
two alleles at most loci
Two main factors controlling simple (single gene) inheritance pedigree patterns
- Chromsomal location of gene (autosomal, X linked (or other) ); male mammals are hemizygous for X
- phenotype expression pattern for allele of interest (dominant or recessive)
Most typical simple modes of inheritance
- Autosomal dominant
- Autosomal recessive
- X-linked dominant
- X- linked recessive
Blood types
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
A phenotype
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
AB phenotype
express both A oligosacharides and B oligosaccharides on cell surface so both are immune-reactive so they are co dominant
A B and O forms genetic differences
- 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
P (A or B)=
P(A)+P(B)= 100%
so long as events A and B are mutually exclusive (only one can occur at a time)
many recessive disorders are
enzyme defects where proper fx of single normal allele can prevent clinical problems
Dominant disorders can result from
haploinsufficency, dominant negative effect, and gain of function
haploinsufficency
single normal allele is not sufficient to produce normal phenotype
dominant negative effect
altered gene product antagonizes normal product
gain of function
changing the gene product’s specificity or expression pattern rather than reducing or eliminating it (ex oncogene Ras confers a dominant predisposition to cancer)
P (A and B)=
P (A) x P(B)
outcome of A does not effect outcome of B (they are independent)
Pedigree analysis
Male= box Female= circle diseased= filled in undiseased= unfilled deceased= line through
Autosomal dominant inheritance
- 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)
Autosomal recessive inheritance
- 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)
chances of a phenotypically normal offspring of two heterozygous parents for autosomal recessive being carrier
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)
X linked inheritance
- 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
X inactivation
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
X linked dominant inheritance
- 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
1/3000 male cats is calico
kleinfelters syndrome (xxy)
X linked recessive inheritence
- 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
monogenic disorders
dictated by single gene
polygenic disorders
dictated by multiple genes
can you have insufficient information from pedigree analysis to determine mode of inheritance
yes in which case write that there is insufficient info
