[01.03a] Principles of Genetics & Overview of Genetic Pathology

Familial

Hereditary disorders are derived from one’s parents and transmitted in the germ line, also known as?

“Born with” or “present at birth”

What does the term congenital mean?

Monogenic/Single Gene/Mendelian Disorders

What type of genetic disorder is characterized by a mutation in single genes with large effects and often follows Mendelian inheritance?

Pleiotropy

What term describes when a single gene mutation has many phenotypic effects, as seen in Marfan syndrome?

Interactions between multiple genetic variants and environmental factors

Complex Multigenic Disorders are caused by what?

Polymorphism

Variations of genes common in the population are called?

Somatic cells

Mutations that are not transmitted to progeny arise in what type of cells?

Permanent changes in the DNA

What are mutations?

Germ cells

If a mutation occurs in these cells, it can be passed down to progeny?

Single point mutation/substitution

What type of mutation involves a change in only one nucleotide in the DNA?

Missense mutation

What type of single point mutation within coding sequences may replace an amino acid?

Nonsense mutation

What type of point mutation changes a codon to a “stop” codon, leading to a truncated protein?

Intron mutation

Mutations within non-coding sequences that may interfere with transcription factor binding are called?

Frameshift mutation

What type of mutation occurs when deletions or insertions involve base pairs not in multiples of three?

Amplifications (repetition) of a sequence of three nucleotides

Trinucleotide-repeat mutations are characterized by what?

Huntington’s disease

What disease is characterized by repeating CAG trinucleotide repeats?

Fragile X Syndrome

What condition is associated with more than 230 CGG trinucleotide repeats?

Maternal inheritance

Mutations in mitochondrial DNA (mtDNA) are passed down through which parent?

Cardiomegaly

What prominent clinical feature is associated with Pompe Disease (Type II Glycogen Storage Disease)?

Codominance

What term describes when both alleles of a gene pair contribute to the phenotype, such as in ABO blood groups?

Single mutant gene has many effects

What is pleiotropism?

Mutations at several loci produce the same trait

What is genetic heterogeneity?

Autosomal dominant inheritance

Which transmission pattern describes a condition manifested in the heterozygous state, where at least one parent is usually affected?

Reduced penetrance

What term describes when persons inherit a mutant gene but are phenotypically normal?

Variable expressivity

What term describes when a mutant gene is expressed differently among persons carrying the gene, such as in Neurofibromatosis 1?

Coarse facial features, clouding of cornea, joint stiffness, mental retardation

What are four general characteristics of Mucopolysaccharidoses (MPS)?

Both sexes are affected and generations are not skipped

What are two key characteristics of an autosomal dominant pedigree?

Autosomal recessive inheritance

Which category of Mendelian disorders requires both alleles to be mutated for a manifestation to occur?

Carrier state

If only one mutant allele is present in an autosomal recessive disorder, what is it considered?

Almost all inborn errors of metabolism

What class of disorders does autosomal recessive inheritance commonly include?

Sickle cell anemia

What hematopoietic disorder is an example of an autosomal recessive condition?

Affected individuals often have unaffected parents who are carriers, males and females are equally affected, and generations may be skipped

What are three key characteristics of an autosomal recessive pedigree?

X-linked

All sex-linked disorders are what type of linked inheritance?

Males

In X-linked recessive inheritance, which sex usually manifests the disease due to only needing one copy of the mutated X-gene?

Hemophilia A and B

What blood disorders are examples of X-linked recessive conditions?

All daughters affected, sons normal

If an affected male with an X-linked dominant disorder mates with a normal female, what is true about their children?

Enzyme replacement therapy, substrate reduction therapy, molecular chaperone therapy

What are three general approaches to treatment for lysosomal storage diseases?

Marfan Syndrome

What is a disorder of connective tissue principally involving the skeleton, eyes, and cardiovascular system, caused by a defect in fibrillin-1?

Defect in extracellular glycoprotein FIBRILLIN-1

Marfan Syndrome is caused by an inherited defect in what?

Ectopia lentis

What ocular finding, described as bilateral subluxation or dislocation, is almost always indicative of Marfan syndrome?

Hyperextensible skin and hypermobile joints

What are the classic signs of Ehlers-Danlos Syndrome?

Mutations in the gene encoding the LDL receptor (LDLR gene)

Familial Hypercholesterolemia is most commonly caused by what?

Class III

Which class of Familial Hypercholesterolemia is characterized by the LDL receptor failing to bind LDL, affecting the ApoB binding site?

Lysosomal storage diseases

Tay-Sachs, Niemann-Pick, Gaucher, and Mucopolysaccharidoses are examples of what type of disease?

Accumulation of partially degraded insoluble metabolite

What is a common consequence of a deficiency in a functional lysosomal enzyme?

Tay-Sachs Disease

What lysosomal storage disease is characterized by a deficiency in β-hexosaminidase, leading to the accumulation of GM2 gangliosides and a cherry red spot in the macula?

Ashkenazi Jews

Tay-Sachs disease and Niemann-Pick diseases are prevalent in what population group?

Sphingomyelin

Niemann-Pick diseases are characterized by the lysosomal accumulation of what substance?

Gaucher Disease

What is the most common lysosomal storage disease, caused by a mutation in the gene encoding glucocerebrosidase, leading to "crumpled tissue paper" appearance in macrophages?

Parkinson’s disease

Mutation of the glucocerebrosidase gene is the most common known genetic risk factor for what neurological disorder?