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Flashcards in Exam V Deck (27):

Autosomal Recessive Disorder



Autosomal Dominant Disorder

Achondroplasia (FGFR3 mutation) - stops bone growth when active causing dwarfism; Homozygotes (usually lethal) more severely affected than heterozygotes

homozygous for the disease = usually lethal



males are hemizygous for all genes on the X chromosome
they only have one allele and can’t be homo or heterozygous


X-linked Dominant Disease

affected males and homozygous females are usually lethal
females are twice as likely to get the disease than males
sons get the disease from mother only and females can get the disease from either parent

Hypophosphatemic rickets
Kidneys can’t reabsorb phosphate
Abnormal ossification, bones bend and distort

Incontinentia pigmenti
Abnormal skin pigmentation and teeth
Neurological and ocular abnormalities
Males lost in utero


Variable Expression

The range or intensity of the trait in question. The severity of symptoms can vary from person to person, for example, in single-gene disorders such as cystic fibrosis and sickle cell disease and in common, complex disorders such as major depression and diabetes.


Allelic Heterogeneity

In some instances different alleles at the same locus cause the same disorder, a situation called allelic heterogeneity. A notable example is cystic fibrosis, where more than 600 different alleles can cause the associated symptoms.
Sickle Cell Anemia does not show allelic heterogeneity because always caused by the same mutation


Compound Heterozygosity

the two different abnormal alleles together knocks out the same gene because they are at the same locus (location) of the maternal and paternal chromosomes given to the offspring


Locus Heterogeneity

Different mutations in different chromosomes causing the same disease
Contrast allelic heterogeneity with a situation where mutations in genes at different loci cause the same disease. An example of this locus heterogeneity is familial hypercholesterolemia, a single-gene disorder that causes very high cholesterol levels and high risk for coronary artery disease. Mutations in the APOB and LDLR genes are the most common cause of familial hypercholesterolemia, though other genes have been implicated.



proportion of individuals with the relevant genotype who show the phenotype. Usually expressed as a percentage.
a. Example: Split-Hand Deformity (Ectrodactyly) Shows Reduced Penetrance



single gene has multiple effects ex. CF


Fragile X Syndrome

Most common inherited form of mental retardation
Down syndrome more common, but not inherited
Fragile refers to effect in cultured cells
End of long arm of X breaks in low folic acid
Affects 1/4000 males, 1/8000 females
Not recessive, not fully dominant


Sherman Paradox

Transmitting male will have a daughter that is not affected but the repeats will expand during her meiosis so then if the daughter has a grandson then he could be affected because the expansion of the repeats causes silencing
Repeat expands only in female meiosis
Offspring of transmitting males have same number as father
More than 230 repeats– the gene is silenced by methylation then you have the full blown phenotype because you are losing transcription
example: Fragile X syndrome; Long face, prominent jaw, large ears and similar across ethnic groups


Holandric Inheritance

Father to son (Y linked): Most genes involved with sex determination, spermatogenesis, testicular function

Male limited: can be autosomal or sex linked disease but only affects males


Mitochondrial Disorders

can only be passed by mother to offspring
since many mitochondria per cell, the mutation may be present in only some of them (heteroplasmy)
percentage of mutations = severity of disease
1. Leber hereditary optic neuropathy (LHON)
Optic nerve death in 3rd decade (20s)
Heteroplasmy uncommon, pedigrees simple
Missense mutation in protein coding genes
2. Myoclonic epilepsy with ragged red fibers (MERRF)
Single base changes in a tRNA
Epilepsy, ataxia, dementia, myopathy
Heteroplasmic, highly variable expression



Phenotypic trait or condition
Induced by environmental factors 
Closely resembles a phenotype usually determined by genes 
It is not inherited, not given to offspring
Examples of phenocopy include conditions caused by somatic mutations or infections during pregnancy:
Cretinism (congenital hypothyroidism  short stature + mental retardation)
Mental retardation 
Congenital cataracts (rubella virus infection during pregnancy) 


Multifactorial Inheritance (MI)

Polygenic: Influenced by multiple genes
Environmental factors influence
Normal bell shaped distribution
When quantification on a continuous numerical scale is possible
Examples: Human height, weight, and blood pressure
Atopic reactions (allergies), Alzheimer's, alcoholism, schizophrenia, bipolar disorder, coronary heart disease, congenital malformations, hypertension, diabetes, cancer, cleft lip & cleft palate, congenital hip dysplasia, club foot, pyloric stenosis, spina bifida, anencephaly: brain development defect resulting in small or missing brain hemispheres


Liability and Threshold

MI goes by increased liability meaning an accumulation of several genetic traits until you reach a threshold then you will see a phenotype
Liability – basis for disease; accumulation of defected genes
Threshold – amount of defected genes (liability) that will cause disease once you pass a certain amount; if you have less than the threshold, you will not have the disease, but dangerous for the offspring because you pass on these defected genes on and they can reach the threshold in the offspring
Example: Pyloric stenosis
Presents at birth caused by a narrowing of the pylorus leading to chronic vomiting, constipation, weight loss, electrolyte imbalance; more common in males
Male : Female = 5:1


Recurrence Risk

The probability of giving birth to an affected child in a family which already produced one affected child or more
more predictable for single gene diseases
Autosomal dominant: 50% (heterozygote + normal homozygote)
Two affected heterozygotes: 75% affected and 25% unaffected
For Medelian: Recurrence risk is the same for everyone
For MI: Recurrence risk is increased when family members are affected
Increases: With the number of affected children in a family, with severity of the defect, a more severely affected parent is more likely to produce an affected child


Twin and Adoption Studies

Genes (twin) and environment (adoption separately) relative influence on disease development
Preliminary indications about genes involvement
These studies do not provide:
Identification of specific genes responsible for disease
Definitive measurement of the role of genes


Concordance Rate

The presence of a given trait in both members of a pair of twins
For concordant traits
Concordance of 1.0 in MZ
Concordance 0.5 in DZ
For 100% environmental traits:
Both DZ and MZ have similar concordance rates


Mendel vs. Galton

Mendel: Studied discontinuous characters ("either/or" traits) green peas vs. yellow peas, tall vs. dwarf
No overlap of phenotype in Mendel's studies
Characters fit into one of two classes
No blending in the heterozygote

Galton: Studied inheritance of continuous characters
Height in humans, intelligence in humans
Extremely tall fathers tend to have sons shorter than themselves and extremely short fathers tend to have sons taller than themselves
"Tallness" or "shortness" are non-Mendelian
Offspring seem to regress to the median- "mediocrity"



Galton was the founder of eugenics
Genetics as tool of human breeding
Intelligence inheritance is not different from tallness:
Both are quantitative, multifactorial traits
They are not qualitative, single gene traits
Breeding mediocre intelligence must have been a huge disappointment for eugenicists
basically you can't breed two intelligent people to get more intelligent offspring


Fisher Punnett Square

Made inheritance of quantitative traits look like Mendelian inheritance at multiple loci
3 loci with 3 alleles each = bell shaped curve/Gaussian distribution



Regression towards the mean - tall man + average women = son in between those height because the mother "diluted" the genes

Tallness gene in woman is 3" shorter than the same gene in a man, so if there is a couple that are the same height the offspring can be taller than both of their parents


Unimodal MF (multifactorial) vs. Bimodal SGM (single gene modal)

UM-MF is environment + genes and the threshold theory explains why sometimes things are not expressed or expressed (unimodal); Gaussian distribution; ex. cleft palate - you either do or don't have the trait there is no intermediate and the threshold theory explains this

BM-SGM is just genes and something can only be one or another NOT MI (bimodal); single gene with dominant/recessive alleles; modifying environmental factors



increases the probability of an affected child for a multifactorial trait
related individuals increase the risk by 2 fold for MI diseases compared to unrelated individuals


Type I Diabetes

MI disease
An islet of Langerhans demonstrates insulitis with lymphocytic infiltrates in a patient developing type I diabetes mellitus. Could be viral
Concordant risk in MZ twins for Type I is 0.35-0.50 indicating other non-genetic factors are involved
Type I is associated with the MHC alleles HLA DR3 & DR4- inappropriate expression causes T cell attack on B cells of islets in pancreas
Polymorphism in the 5’-end of the insulin gene accounts for 10% of the familial clustering of type I diabetes.
An increased number of tandem repeats affects transcription of the insulin gene