Chapter 5- Genetic Disorders Flashcards by Taylor Horlock

What types of mutations are highly penetrant and follow classic Mendelian inheritance patterns?

Single genes with large effects

How well did you know this?

Not at all

Perfectly

What are the most common cause of genetic disorders?

Multi-genetic disorders

How well did you know this?

Not at all

Perfectly

What is a mutation?

Permanent change in DNA

How well did you know this?

Not at all

Perfectly

What is the difference between a germ cell and somatic mutation?

Germ cell- transmitted to offspring

Somatic- not transmissible

How well did you know this?

Not at all

Perfectly

What kind of mutations are there?

Coding
Non-coding- enhancer or promoter
Frameshift
Trinucleotide repeat- amplification of triplet nt sequences

How well did you know this?

Not at all

Perfectly

What are the two kinds of point mutations?

Missense- single nt substitution changes the triplet base code
Nonsense- single nt substitution creates a stop codon

How well did you know this?

Not at all

Perfectly

What are the two types of missense mutations?

Conservative- protein structure remains

2. Nonconservative- change affects the final protein structure

How well did you know this?

Not at all

Perfectly

What is penetrance?

The percentage of individuals that carry the gene AND express the trait

How well did you know this?

Not at all

Perfectly

What is variable expressivity?

Variation in the effect caused by the mutation (expression varies among individuals)

How well did you know this?

Not at all

Perfectly

What is pleiotropism?

Multiple possible end effects of a single mutation (expressions within a person varies)

How well did you know this?

Not at all

Perfectly

What is genetic heterogeneity?

Multiple different mutations can lead to the same outcome

How well did you know this?

Not at all

Perfectly

What are the different transmission patterns of single gene disorders?

Autosomal dominant- LOF
Autosomal recessive- complete penetrance, metabolism errors
X-linked- sex linked recessive, fully expressed in men

How well did you know this?

Not at all

Perfectly

What are the consequences of enzyme defects?

Reduced synthesis

Toxic substrate accumulation

Decreased end product

Decreased substrate metabolism

Defects in receptors and transport

Alterations in non-enzyme proteins

Adverse drug reactions

How well did you know this?

Not at all

Perfectly

What disorders are associated with structural proteins?

Marfan syndrome

Ehlers-Danlos syndrome

How well did you know this?

Not at all

Perfectly

What are the characteristics of Marfan syndrome?

Mutation in 15q21.1 (fibrillin-1 gene)

Affects skeletal, ocular, CV and integumentary systems

Tall, long extremities, scoliosis

How well did you know this?

Not at all

Perfectly

What are the characteristics of Ehlers-Danilo’s syndrome?

Defect in collagen synthesis

Fragile skin and poor wound healing

Hyper mobile joints

How well did you know this?

Not at all

Perfectly

What are the characteristics of familial hypercholesterolemia?

Mutation in LDL receptor

Loss of feedback control (increased circulating cholesterol)

How well did you know this?

Not at all

Perfectly

What disorders are associated with enzyme defects?

Lysosomal storage diseases

Tay-Sachs disease

Niemann-Pick

Gaucher disease

Mucopolysaccharidoses

Glycogen storage diseases

Allaptonuria/ochronosis

How well did you know this?

Not at all

Perfectly

What are the characteristics of lysosomal storage diseases?

Accumulation of partially degraded metabolites

Enlarged lysosomes

Lack of autophagy

What are the characteristics of Tay-Sachs disease?

Hexosaminidase deficiency inhibits ganglioside catabolism

Neurons most affected

Oil red O and Sudan black pos

Whorled lysosome

Cherry red spot in macula

What are the characteristics of Neimann-Pick disease?

A (infantile) and B- sphingomyelin accumulation

C- defect in nonenzymatic lipid transport

What are the characteristics of Gaucher disease?

Reduced glucocerebrosidase activity (accumulation)

PAS pos

What are the different types of Gaucher disease?

I- mononuclear phagocyte involvement

II- CNS involvement, infants

III- involves both macrophages and CNS

What are the characteristics of mucopolysaccharidoses?

Deficiency in enzymes that degrade glycosaminoglycans

Coarse facial features, mental retardation, corneal clouding valve and sub-endothelial arterial thickening

What are the two forms of mucopolysaccharidoses?

Hunter- x-linked recessive Hurler

What are the three forms of glycogen storage diseases?

1. Hepatic- catabolism deficiency 2. Myopathic- glycolysis enzyme deficiency 3. Miscellaneous- alpha-glucosidase deficiency, glycogen overload in many organs (Pompe=cardiac involvement)

What are the characteristics of alkaptonuria/ochronosis?

Decreased homohentisic oxidase Blocks phenylalanine metabolism Homogentisic acid accumulation Blue-black pigment

What are polymorphisms?

Genes with at least two alleles (one has a frequency >1%)

What are the numerical chromosomal disorders?

Monosomy Trisomy Mosaicism- different cell populations

What are the structural chromosomal disorders?

Deletions Translocation- balanced/reciprocal or Robertsonian/centric Isochromsome- deletion and duplication Inversion- paracentric or pericentric Ring chromosome

What are the different types of cytogenic autosomal disorders?

Trisomy 21 (Down syndrome) Trisomy 18 (Edward’s syndrome) Trisomy 13 (Patau syndrome) Chromosome 22q11.2 deletion syndrome (diGeorge and velocardiofacial) Cri du chat (5p deletion)

What are the characteristics of Down syndrome?

Extra chromosome 21 Due to maternal age or Robertsonian translocation Flat face, epicanthic folds, congenital heart disease

What are the characteristics of Edward’s syndrome?

Extra chromosome 18 Mental retardation Micrognathia, overlapping fingers, congenital heart defects, renal malformation

What are the characteristics of Patau syndrome?

Extra chromosome 13 Microcephaly, mental retardation Microphthalmia, polydactyly, cleft palate, cardiac and renal defects

What are the two forms of chromosome 22q11.2 deletion syndrome and their characteristics?

DiGeorge- thumping hypoplasia, T cell deficiency Velocardiofacial- congenital heart disease

What is the Lyon hypothesis?

One x-chromosome is randomly selected to be inactivated Mosaicism seen in females

What is a Barr body?

Inactive X-chromosome

What is SYR?

Sex determining region on a Y chromosome

What are the cytogenetic disorders involving sex chromosomes?

Klinefelter syndrome (2+X and 1+Y) Turner syndrome (monosomy of X)

What are the three different types of trinucleotide repeat mutations?

Fragile X- CCG repeats during oogenesis Huntington disease- CAG repeats during spermatogenesis Friedreich’s ataxia- GAA repeats in FXN gene (LOF)

Why is the expression of mutations in mitochondrial genes unpredictable?

Cell can contain both normal and mutant mtDNA Heteroplasmy- proportions during division are random

What is genomic imprinting?

Epigenetic process resulting in differential inactivation of either maternal or paternal alleles if certain genes

What are the two disorders of genomic imprinting?

1. Prader Willi- q12 deletion in chromosome 15 from father | 2. Angelman- q12 deletion in chromosome 15 from mother

How does gene silencing occur?

Methylation

What is gonadal mosaicism?

Mutation in gonadal cells early in embryonic development Disease can be passed on