Developmental Genetics + Clinical Genetics + Genetic variations Flashcards Preview

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Flashcards in Developmental Genetics + Clinical Genetics + Genetic variations Deck (61)
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Structural variation vs substitution variation

Structural: In/dels

Substitution: SNPs


Common vs Rare variant

Common: both alleles @ +1% frequency

Rare: allele present @ less than 1% frequency


SNP definition

Less common allele of a single nucleotide substituition is present @ +1%

Usually bi-allelic

If muation is in coding region, usually silent or conservative missense


Sickle cell anemia mutation

Glu6 >> Val6 (missense)


Beta thalassemia mutation

Glu6>>STOP (nonsense)


Non coding region mutations can occur in __, __ and ___.

Give 2 examples of this

Promoter, enhancer/silencer, 5' and 3' UTR

Beta thalassemia mutation in promoter region

Repeats in CFTR gene (Intron 8)


Structural variants: What are the 2 ways you could get CF?

Phenylalanine deletion at position 508

(TG)n(T)n repeats in Intron 8 >> exon exclusion of Exon 9


How do repeats that cause Huntington's disease and Fragile X syndrome vary in terms of phenotype + which repeat? (HD)

HD: CAG repeat

Fragile X: CGG

HD: CAG repeats in ORF; more repeats = earlier age of onset

Fragile X: repeats in 5' UTR = loss of function


Fragile X repeat phenotype


Copy number variants: what's the effect of a mutation in the AMY (amylase) gene?

More copies = faster carbohydrate breakdown + improved glycemic homeostasis/decreased diabetes risk


Use alpha thalassemia to explain copy number variations

Repeats can become misaligned, results vary based on mutation (nonsense >> 1/2 normal, missense >> 1/4 normal)



How does an inversion cause hemophilia?

Mispairing of similar factor 8 sequences


Genotype and phenotype correlation:Osteogenesis imperfecta (what's the effect of a missense vs a nonsense mutation?)

Missense: 1/4 normal

Nonsense: 1/2 normal


What is a frameshift mutation?

Frameshift is an inserted or deleted fragment that is not divisible by 3


Explain why a deletion of Exon 45 in the DMD gene would lead to classical DMD but a deletion in a larger fragment will lead to Becker's Muscular Dystrophy (a much milder disease)

The DMD gene is such that each segment contributes to a protein that on the whole will act as a shock absorber (a lot of individual components lined together). A del in Exon 45 (total number of genes NOT divisible by 3) will disrupt the remainder of the gene, thereby destabilizing all the other pieces of the protein/shock absorber. A del in a larger chunk of genetic material, however, would cause less damage b/c the remaining exons would still be translated to functional pieces of the shock absorber thus some function would be retained.


Disease associated (susceptibility) variants:

The MATP gene codes for ___. A mutation in this gene could lead to ___, resulting in___.

Melanin production.

Lighter skin.

Vitamin D deficiency/Malignant malinoma


A lower copy number of an AMY mutation could lead to___

Increased predisposition to obesity


Malformation definition

Damage that results from intrinsic GENETIC abnormalities


Major malformation

If uncorrected/incorrectable, defect impairs normal function/reduces life expectancy


Minor malformation

Defect that is of mostly cosmetic significance


Major malfomation examples


 cleft lip +/- palate


Fetal alcohol syndrome

Trisomy 13



Fetal alcohol syndrome cause + symptoms

Cause - Teratogen

Symptoms - 

Thin upper lip

Growth retardation

Learning disabilities

Smooth philtrum


Cleft lip +/+ palate characteristics

More common in males than females

Usually isolated

One of the most common multifactorial birth defects


Cleft palate

More common in females more than males

Usually syndrome-associated

Not as common


Isolated malformation

Restricted to one part of the body


What are the risks of having 3+ minor malformations?

Increased chance of dysmorphic syndrome

Increased risk of major malformation


Syndrome definition

Condition in which one causative agent affects multiple organ systems simultaneously


Pattern of malformations that either are or have to be etiologically related


Waadernburg syndrome characteristics + symptoms

Cause: Type I and 3 = Pax3 mutation (NC cells); Type 2 = MitF mutation (melanocytes)

Phenotype: Skin pigmentation issues

Pale eyes

White patch of hair

+ Upper limb abnormalities if Type 3

+ Hearing loss if Type 2



Sequence definition

Chain of developmental malformations (one leads to the other) resulting from single causative agent


Pierre-Robin sequence

"The small chin baby"

Small mandible

Tongue pushed back

U shaped cleft palate