Patterns of Inheritance Flashcards
locus
segment of DNA at a specific location
alleles
alternative variants of a gene
wild-type
single prevailing allele present in the majority of individuals (depends on population)
variants
mutants; gene other than WT
polymorphisms
variant alleles; may affect disease susceptibility
mutations
new genetic changes in a family or disease–cause mutant alleles
“non-gene” regions
non-protein coding RNAs lie in intergenic regions (within introns) –miRNA/lincRNA
genotype
entire set of alleles in a genotype or set of alleles at a specific locus
phenotype
observable expression of a genotype as a morphological, clinical, cellular, or biochemical trait
homozygous
individuals 2 alleles are FUNCTIONALLY identical at a specific locus
heterozygous
2 alleles are FUNCTIONALLY different
hemizygous
only 1 allele of a gene (men = X chromosome)
compound heterozygous
2 heterogoenous recessive alleles at a particular locus that cause genetic disease in a heterozygous state
pedigree
graphical representation of the family tree
kindred
extended family depicted in pedigree
proband
1st affected person brought to clinical attention (can be multiple)–analyze all other family members in relation to the proband
consultand
person who brings the phenotype to clinical attention (can be affected or unaffected individual)
first degree relatives
parents, siblings, offspring of proband
second degree relatives
grandparents, grandchildren, nieces, nephews, half-sibs
third degree relatives
first cousins
relative degree assignments
first, second, third, etc based on NUMBER OF STEPS in the pedigree between the two relatives
consanguineous
couples sharing 1+ ancestor in common; closely related (2nd cousins or closer)
fitness
genetics term; refers to the measure of the impact of a condition/genotype on reproduction–defined by number of offspring who survive to reproductive age compared to a control group
vertical transmission
transmission of a disease from one generation down to the next; implies family history of disease; excludes sporadic cases
mosaicism
X-linked disorders; females randomly inactivate 1 X-chromosomes in each cell; phenotypic expression only in a subset of cells
pure dominant
both homozygotes and heterozygotes show identical severity of phenotype
semidominance
disease is more severe in homozygotes than heterozygotes–incomplete dominance–more common
codominant
2 different allels are expressed together (ABO)
penetrance
probability that a mutant gene will have any phenotypic expression
reduced penetrance
When the percent of individuals with a mutant genotype demonstrating some disease phenotype is less than 100%
expressivity
severity of expression of the phenotype in individuals with the same disease-causing genotype
variable expressivity
when severity of a disease differs in people who have the same genotype
congenital disease
phenotype recognized at birth
late-adult onset
common way that severe autosomal dominant disease can continue to be passed on; don’t show up until after individual has reproduced (Huntington’s)
allelic heterogenity
different alleles caused by different mutations of the SAME GENE result in varying disease phenotype; depending on severity of mutation, you get a range of different phenotypes
locus heterogeneity
disease phenotype is caused by mutations in distinctly DIFFERENT GENES
CFTR
allelic heterogeneity
phenotypic heterogeneity
different mutations in SAME GENE cause completely DIFFERENT DISEASES
RET gene mutation
phenotypic heterogeneity; causes dominantly inherited Hirschsprung and endocrine cancers
autosomal recessive inheritance
occurs in mutant homozygotes or compound heterozygotes; no normal alleles
sex influenced autosomal recessive inheritance
NOT X-linked recessive; both sexes develop the disease, one sex just has a higher frequency (increased penetrance)
inbreeding
similar to consanguinity, but at the population level; describes individuals from a small pop. tending to choose their mates from within the same population (cultural, geographic, or religious influence)–>share gene alleles from ancestors (increasing homo. recessive disorders)
likelihood of new mutations in autosomal dominant disorders rises dramatically with ____ of the parents
age
Sex-limited phenotypes in autosomal dominant disorders
Different from X/Y-linked–can be mapped to an autosome and has direct father-son transmission; trait is seen ONLY in one sex; male-limited precocious puberty
Precocious puberty
male-limited sex-limited autosomal dominant disorder
Hemophilia A
X-linked disorder
Purpose of X-inactivation
dosage compensation for expression of X-linked genes
How do you determine if X-linked disorder is recessive or dominant?
Phenotype of heterozygous females; if consistently expressed in carriers = dominant
Manifesting heterozygotes
X-linked recessive female carriers show some abnormalties in phenotype (severity depends on what the target tissue is)
If an affected males’ daughters are all affected, but his sons are not, what is the inheritance pattern?
X-linked dominant inheritance (females have to have X from father–has to be mutant; males get normal Y)
Only females exhibit disease; sons that exist are normal phenotype:
X-linked dominance with male lethality (living males received WT X from mother)
Mutational Mosaicism
can occur from early development when clone of cells develops from a single mutation; these cells go on to form a tissue or part of tissue that is abnormal
Mitochondrial Disorders
only inherited from mother; both male and female offspring have equal presentation of disease
