Genetic Disease Flashcards
___ pairs of autosomes and ___ pair of sex chromosomes.
22; 1
23 pairs of total chromosomes
normal chromosome count is 46
Roughly ___ protein-encoding genes in the human genome.
19,000
What results in mutation?
alteration in the genetic code (A,C,G,T)
T/F. Mutations of a certain gene locus may affect one or both of the chromosomes in a pair.
True.
Define heterozygous and homozygous.
When one chromosomal locus in the pair is affected, the individual is heterozygous for the disorder; if the loci of both chromosomes have the mutated gene, the individual is homozygous.
What refers to a permanent change in the DNA? What happens if a mutation affects germ cells vs somatic cells?
Mutation.
Those affecting germ cells can be transmitted to progeny.
Those affecting somatic cells can result in tumors or developmental malformations.
What is the difference between point (missense), frameshift, and trinucleotide repeat mutations? Give an example of each.
Point mutations (missense mutation) – single nucleotide base substituted. Example: sickle cell anemia Frameshift mutations – insertion or deletion of one or two base pairs, altering reading frame of the DNA strand (early stoppage of reading frame) Trinucleotide repeat mutations – amplification of sequence of 3 nucleotides. Example: Fragile X syndrome
What percentage of neoplasia is inherited?
5-15%
What else can alter protein-coding genes other that mutations?
- polymorphisms
- Epigenetic Changes
- Alterations in non-coding RNAs
Single nucleotide ___ – variation in just one nucleotide (for example, A or T) at a single site on the DNA molecule. Over 6 ___ have been identified, but most are within ___, ___ or intergenic regions.
polymorphism; million; exons; introns
May be markers for multigenic complex diseases, such as diabetes or hypertension.
Polymorphisms also include ___ ___ ___, which are different numbers of large contiguous stretches of DNA, from ___ to ___ of base pairs. About half involve ___-coding sequences, and this may account for much phenotypic variation.
Copy number variations; 1,000; millions; gene
What refers to modulation of gene expression without altered DNA sequence?
Epigenetic changes
Important in development as well as normal homeostasis.
With epigenetic changes, ___ of ___ residues on promoter regions makes them inaccessible to RNA ___, thus reducing protein synthesis.
methylation; cytosine; polymerase
What inhibits the translation of their target messenger RNAs into their corresponding proteins.
Micro-RNAs (miRNA’s)
These can control transcription and can “silence” tumor suppressor or apoptotic mechanisms.
T/F. Mendelian disorders are single-gene defects in which one of 2 alleles are affected.
True
What consist of a series of genes? Genes contain information to produce ___ that perform specific functions.
Chromosomes; proteins
Genetic alteration (mutation) often results in production of abnormal protein, which can alter what?
phenotype
Because genes are comprised of many ___ ___, a mutation can occur at different places within the gene, yet produce essentially the same ___ alterations.
base pairs; phenotypic
T/F. Mutations of a gene locus will affect only one chromosome in a pair.
False, Mutations of a gene locus may affect one or both chromosomes in a pair.
Which of the following is INCORRECT about autosomal dominant disorders?
- Mutated gene on one of the autosomes
- Expressed in heterozygous state, both parents usually affected
- Often present with outward physical changes and the onset is always present from birth, (e.g., Huntington’s disease).
- correct
- Expressed in heterozygous state, ONE parent usually affected
- Often present with outward physical changes, but these may have delayed age of onset even though the mutant gene is present from birth, (e.g., Huntington’s disease).
With autosomal dominant disorders, both ___ and ___ can have the disorder and transmit the mutant gene. Approximately ___ of the offspring will have the disease if only one parent is affected.
males; females; half
Define reduced or incomplete penetrance.
If a person has a mutant gene, but doesn’t or only partially expresses it phenotypically
___ ___ occurs if expression can be identified in all affected persons, but to differing extents.
Variable expresivity
T/F. If neither parent affected and there is no family history then the autosomal dominant disorder is termed new or a “de novo” mutation.
True.
Neurofibromastosis is a ___ ___ disorder with nearly ___% penetrance. It has highly ___ ____.
autosomal dominant; 100%; variable expressivity
nearly everyone who has this mutation will show evidence of this relatively common (1/3,000 live births) condition
T/F. Autosomal dominant disorders are the largest group of mendelian disorders.
False, autosomal RECESSIVE disorders are the largest group of mendelian disorders.
T/F. With autosomal recessive disorders the trait is expressed only if both genes at a
given locus are affected (homozygous individuals).
True, two germline mutations (one from each parent)
Does the parent of an individual affected with an autosomal recessive disorder show the disease?
No
With autosomal recessive disorders, what percentage of offspring of heterozygous carrier parents are affected? Carriers?
Affected (homozygous dominant) - 25% ( 1 in 4 chance) a HORIZONTAL pattern in family
Carriers (heterozygous) - 50% (2 in 4 chance)
What could be the cause of the appearance of a rare autosomal recessive disease?
If the mutant gene is rare, there is a strong probability that the affected child (proband) is the product of a consanguineous relationship.
