Terms for Patterns of Single gene inheritance

Question 1

What is a Single gene disorder?

Answer 1

• Single defective allele @ locus

- Appear mostly at pediatric/pre-natal

Question 2

Polymorphism

Answer 2

• Occurrence of 2 or more normal alleles @ a locus

- Normal variants due to harmless mutations

Question 3

Compound Heterozygote

Answer 3

-An indiv. or genotype w/2 different mutant alleles @ given locus.

Question 4

Incomplete dominance

Answer 4

• phenotype due to heterozygous genotype is different from both homozygous genotypes.
• Severity is intermediate between both homo. phenotypes

Question 5

Recessive

Answer 5

-Trait or gene NOT phenotypically expressed in Heterozygotes

Question 6

What are the 4 types of single gene inheritance patterns?

Answer 6

• Autosomal: Dominant & Recessive

- X-Linked: Dominant & Recessive

Question 7

What is an Index Case/Proband/Propositus?

Answer 7

-An affected family member who is Pt. zero in pedigree for genetic abnormality

Question 8

2 Characteristics of autosomal dominant

Answer 8

1. Reduced penetrance (carrier/all or none/skip generations)

2. Variable Expressivity (severity of phenotype differs in people with same genotype)

Question 9

What is Genetic Heterogeneity?

Answer 9

• Phenotypes are similar BUT are determined by different genotypes
• Locus: Mutations @ different loci (Ehlers-Danlos)
• Allelic: Different mutations @ same locus (cystic fibrosis)
• Phenotypic: Different mutations @ same gene different phenotypes (Hirschsprung)

Question 10

What is an Autosomal Recessive Inheritance?

Answer 10

• Presents in homozygous state (2 mutant alleles)
• Heterozygotes = healthy carriers (1 mutant allele)
• 2 carrier parents have 1 in 4 chance to have affected offspring
• Male to Male
• Affect female/male same
• Seen in horizontal transmission (siblings) = consanguineous

Question 11

Autosomal recessive & Consanguinity

Answer 11

• Homozygous Affected offspring inherited mutant allele from both parents.
• Parents share common ancestor

Question 12

Autosomal recessive/Sex influenced

Answer 12

• Expressed in both sexes BUT with different frequencies

- Ex. Hemochromatosis (disorder in iron metab. = enhanced iron in body) more common in males and 1/10 for females

Question 13

What is Autosomal Dominant Inheritance?

Answer 13

• Manifests in heterozygous
• Phenotype in EVERY generation = Vertical transmission (affected person has affected parent)
• 50% recurrence risk
• Can arise from a NEW mutation
• Affects males & females (=)

Question 14

Psuedoautosomal region

Answer 14

• region of homology between X & Y chromosomes @ tip of short arms (p)
• Allows X & Y chromosomes to pair properly during meiosis (prophase 1)

Question 15

Holandric Inheritance

Answer 15

-pattern of inheritance from father to son from Y

Question 16

Sex linked inheritance

Answer 16

-Males/Females express X-linked genes equally due to dosage compensation

Question 17

X chromosome Inactivation

Answer 17

• Random and permanent (barr body)
• Done by methylation of CpG dinucleotides in promoter regions
• It is incomplete because some genes escape

Question 18

Non-Random Inactivation

Answer 18

• Structurally abnormal X (deletions, duplications) = Abnormal X shut off
• Autosome translocations (balanced)= Normal X shut off
• Unbalanced translocations = Abnormal X shut off

Question 19

X-Linked Recessive

Answer 19

• Phenotype more common in Males
• Male transmits gene to all daughters (X-X)
• NOT transmitted from father to son
• ex. color blindness

Question 20

X-Linked Dominant

Answer 20

• Commonly affected in heterozygotes
• Affected male + normal mate = all daughters affected & no males affected
• Males are more severely affected –>Death before birth

Question 21

Pseudoautosomal inheritance

Answer 21

• inheritance pattern associated w/genes on pseudoautosomal region of X & Y
• Genes involved in a transcription factor
• Escapes X inactivation

Question 22

Mosaicism

Answer 22

• 2 different cell lines that differ genetically BUT come from a single zygote
• Ex. Chromosome inactivation

Question 23

Somatic Mosaicism

Answer 23

• Mutation occurs early in embryogenesis & affects morphogenesis (growth/development)
• Patchy abnormalities
• Can be picky and affect only certain parts of the body

Question 24

Germline Mosaicism

Answer 24

• Happens in both Male/Female

- So many mitotic divisions probability of mutation is likely

Question 25

Unstable repeat expansions

Answer 25

- Lead to disease by an expansion of repeating units of 3+ w/in affected gene - Genes are wild type that are polymorphic (genes that encode for blood type) - Dynamic mutations (adjust over generations) can be the cause for bacterial resistance - Presents earlier in age from gen. to gen. - Disorders tend to be neurological - Mech. is due to sipped mispairing

Question 26

mtDNA

Answer 26

- Inherited from Mother - Pattern of inheritance is mendelian (affect single loci) - All offspring of affected female will inherit mutated mtDNA. - Mothers w/heteroplasmy (some mutated/some NOT) do NOT transmit mutant mtDNA to offspring

Question 27

Multifactorial/Complex disorders

Answer 27

- Diseases that result from genetic & environmental factors - Familial aggregation - Run in families BUT no mendelian inheritance - Ex. Cancer, Diabetes, Alzheimers

Question 28

Phenotypes for Complex disorders

Answer 28

- Qualitative: Present or absent ex. male/female | - Quantitative: Measurable physiological or biochemical quantities. Ex. BP, height.

Question 29

Familial aggregation & Complex disorders

Answer 29

- Concordant: 2 related indiv. have same disease - Discordant: Only one family member from a pair relatives is affected - Genocopy: Genotype that determines phenotype similar to another genotype - Phenocopy: mimic phenotype of specific genotype BUT comes from interaction w/enviromental factors on normal genotype.