Patterns of single gene inheritance: overview

Question 1

Single gene/Mendelian disorders

Answer 1

single defective allele at a locus, characteristic pedigree, mostly pediatric

Question 2

Locus

Answer 2

gene location on a chromosome

Question 3

alleles

Answer 3

paired genes at a locus

Question 4

wild type allele

Answer 4

normal version of the gene

Question 5

mutant allele

Answer 5

differs from wild type (WT) allele may cause disease

Question 6

polymorphism

Answer 6

two or more normal alleles at a locus

Question 7

genotype

Answer 7

genetic make up of an individual

Question 8

phenotype

Answer 8

the expression of a genotype

Question 9

homozygous

Answer 9

identical alleles at a given locus

Question 10

heterozygous

Answer 10

two different alleles at a given locus

Question 11

compound heterozygote

Answer 11

2 different mutant alleles at a given locus

Question 12

Dominant

Answer 12

expressed in heterozygotes

Question 13

Co-dominant

Answer 13

both alleles of a pair are expressed

Question 14

incomplete dominance

Answer 14

phenotype due to heterozygous phenotype is diff from both homozygous genotypes and severity is intermediate between them

Question 15

Recessive

Answer 15

a trait or a gene is recessive if it is NOT phenotypically expressed in heterozygotes

Question 16

autosome

Answer 16

22 pairs in human karyotype

Question 17

X-linkage

Answer 17

genes on X chromosome; traits determined by such genes are X-linked

Question 18

4 types of single gene inheritance

Answer 18

Autosomal:AD,AR X-Linked: Dominant, recessive

Question 19

pedigree

Answer 19

a diagram of an extended family, indicating their relationship to the pro band, and their status with respect to a particular hereditary condition

Question 20

Proband/Propositus/Index Case

Answer 20

the affected family member through whom the family is brought to attention

Question 21

Pedigree: Consultand

Answer 21

person who brings family to attention by consulting a geneticist

Question 22

Pedigree:Sibs

Answer 22

brothers and sisters; entirety of siblings-sibship

Question 23

Pedigree: Kindred

Answer 23

entire family

Question 24

Pedigree:Relatives- 1st degree

Answer 24

parents, sibs, offspring of proband

Question 25

Pedigree: 2nd degree

Answer 25

grandparents, grandchildren, uncles, aunts, nephews, nieces, half sibs

Question 26

Pedigree: 3rd degree

Answer 26

first cousins

Question 27

consanguineous

Answer 27

couples who have one or more common ancestors

Question 28

Isolated case

Answer 28

if there is only one affected member in a family

Question 29

Sporadic case

Answer 29

disease determined to occur due to a new mutation

Question 30

Factors affecting pedigree patterns

Answer 30

characteristic in AD, but not restricted to them.
2 distinct differences in expression.
Reduced penetrance
Variable expressivity

Question 31

Penetrance

Answer 31

probability that a gene will have phenotypic expression

Question 32

Reduced penetrance

Answer 32

When frequency of expression is less than 100%

ie gene is present, but clinical features are absent: lobster claw formation skipping of generation

Question 33

Expressivity

Answer 33

severity of expression of phenotype

Question 34

variable expressivity

Answer 34

severity of disease differs in ppl who have same genotype-Neurofibromatosis (NF1)

Question 35

Neurofibromatosis (NF1)

Answer 35

neurofibromas-multiple fleshy tumors in skin.
Cafe-au-lait-multiple flat, irregular pigmented spots
Lisch nodules-benign hamartomas on iris of eye.
Less freq-mental retardation, CNS tumors, diffuse plexiform neurofibromas and cancer of nervous system or muscle

Question 36

NF1 gene

Answer 36

17 at q11.2
Neurofibromin is a cytoplasmic protein predom expressed in neurons, schwann cells, oligos, astros, leukocytes.
signaling pathways and assoc to microtubules

Question 37

NF1

Answer 37

penetrance 100%, age dependent, VARIABLE EXPRESSIVITY.\

Question 38

factors affecting pedigree patterns

Answer 38

age of onset-depends on disease
not all are congenital
prenatally lethal
small family size
new mutations
absent/variable expression
other genes and environmental factors
accurate info lacking

Question 39

Heterogeneity

Answer 39

Phenotypes that are similar but are actually determined by diff genotypes
allelic, locus, and phenotypic heterogeneity

Question 40

Locus heterogeneity

Answer 40

mutations at different loci, may be AR,AD, or X-linked. RETINITIS PIGMENTOSA, EHLERS-DANLOS SYNDROME

Question 41

Retinitis pigmentosa

Answer 41

currently 3 X-linked, 12 AD and 5 AR forms

Question 42

Ehlers-Danlos Syndrome

Answer 42

More than 10 different loci associated

Question 43

Allelic hetergeneity

Answer 43

Different mutations at same locus. Cystic fibrosis-mutation in CFTR gene

• severe w/pancreatic insufficiency
• mild w/ pacreatic sufficiency

Question 44

Phenotypic heterogeneity

Answer 44

Different mutations in same gene give rise to strikingly different phenotypes. Ex: mutations in RET gene,

Question 45

Phenotypic heterogeneity examples

Answer 45

mutations in RET gene:
loss of function->Hirschsprung disease, failure of colonic ganglia development: defective colonic motility, severe constipation
Point mutations->activate Tyrosine Kinase->multiple endocrine neoplasia type II

Question 46

Punnett Square

Answer 46

allelic combinations of the gametes->determine genotypes and phenotypic ratio.