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Flashcards in Patterns of Single Gene Inheritence Deck (35):

What is compound heterozygous?

What is hemizygous?

Compound heterozygous is that both alleles are mutated but the mutations are found in different parts of the gene.

Hemizygous - It generally just describes how males only have a single X chromosome. Regarding diseases, in males, having a mutated allele located on the X chromosome.


What is allelic heterogeneity?

It is where different mutations at the SAME locus cause a similar phenotype.

Example: a mutation in the same locus can lead to either nonfunctional CFTR or defective trafficking, both of which phenotypically present with severe Cystic fibrosis.


What is phenotypic heterogeneity?

different mutations in the same gene can lead to very different phenotypes.

It is a measure of severity.


What is locus heterogeneity?

Mutations in different chromosomal loci result in the same variant phenotype.

Example: long QT phenotype can be causes by mutations in more than one gene, potassium channels, sodium channels or structural proteins.


What is pleiotropy?

What is it the opposite of?

One gene affects multiple traits so having a single defect in this would result in affecting multiple organ systems, diverse phenotypes and a variety of signs and symptoms.

One trait affected by multiple genes is polygenic.


Sum up and contrast allelic, phenotypic, loci heterogeneity and pleiotropy

Allelic - different mutations in the same gene = one phenotype

Phenotypic - different mutations in the same gene = many different POSSIBLE phenotypes (basically the opposite of allelic, one phenotype vs many phenotype)
-still one mutation to one phenotype essentially

Locus heterogeneity: mutations on different genes = same phenotype

Pleiotropy: mutation of a single gene = many phenotypic effects.


What are 4 factors that confound pedigree inheritence?

1. Early lethality of disorder - if someone who inherits this dies at an early age, it'd be difficult to know what their inheritence was.

2. Small family size - may skew the conclusions because of chance

3. Variable age of onset, decreased penetrance or variable expressivity.

4. Non-mendelian inheritence


What are the characteristics of an autosomal recessive disorder?

What are the characteristics of a AR pedigree?

1. You must have no Wild type allele and two mutated alleles (either same mutation of compound heterozygote), or hemizygotes

-mutant allele for AR disorders are rare, affect the function of enzymes and reduce or eliminate function of the gene product. (so usually loss of function mutations resulting in enzymes)

2. Parents are unaffected, asymptomatic carriers, the proportion of affected males to females is equal, the risk of giving birth to an affected is 1/4, the phenotype may not be found in parents but it is found in siblings of the affected.


Two heterozygous parents.

What is the risk that a child of either sex is affected?

What is the risk that a child of either sex is a carrier?

What is the risk that a child of either sex is unaffected?

What is the risk that an unaffected child is a carrier?

1. 1/4
2. 1/2
3. 3/4
4. 2/3


What does it mean to be an obligate heterozygote?

It means they must be heterozygous for the mutation. For example their offspring expresses an AR disease. The parents must be at least carriers.


Regarding AR diseases, a father is affected. We are unsure of the mother's genotype. We know that she has an affected sister and both of her parents are unaffected. What is the chance the child will be affected.

So first what is the chance she is a carrier if she is unaffected? (you must exclude the probability she is affected)


What is the chance she would then donate the mutant allele?


2/3 x 1/2 = 1/3


What is carrier frequency and in what three situations that increase the inheritance for an AR disorder also have a high carrier frequency?

Consanguinity - closer than second cousins, increases the chance that both parents are carriers

Inbreeding - individuals from a small population mate with those from the same population

Genetic isolates - like geographically they were isolated and so carrier frequency may be higher for certain diseases. like Tay Sachs in ashkenazi jews


What are the features of an autosomal dominant pedigree?

1. every affected individual has an affected parent and there is no skipping of generations.

2. The number of males is equal to female and there is male to male transmission. (excludes X linked)

3. 1/2 of offspring of an affected individual are affected.

4. Normal siblings of affected individual goes on to produce normal offspring.


What is incomplete dominance?

If parents were heterozygous, what would be the risk that offspring of either sex will be affected?

Referring to AD mutations, those homozygous for the mutation will be more severely affect than the individual that is heterozygous

Example: achondroplasia, familial hypercholesterolemia

3 out of 4 (only bb is not affected).


For Pure AD inheritence, a parent that is bb and Bb

What is the risk an offspring of either sex will be affected?

What is the risk that a phenotypically normal child has the mutant allele?

BB homozygotes are exceedingly rare.


and no chance.


Autosomal dominant disorders can have two exceptions to Mendelian inheritance. What are they?

Reduced penetrance: if a person inherits a mutant allele and doesn't express it (meaning it is not 100% of people who inherit it express it, then that is reduced penetrance)
Penetrance: probability that a mutant gene will have a phenotypic expression
-penetrance can also be age dependent.

Variable expressivity - people have the same genotype but can have varying severity of disease expression


What are sex-limited autosomal traits?

Genes are on both autosomes and the genetic mutations are present in both sexes however,

the phenotype is evident in only one sex. The mutation can be passed down by both sexes but it is a matter of expression.


What is male-limited precocious puberty?

It is an example of sex-limited AUTOSOMAL DOMINANT phenotype.

The mutation in the luteinizing hormone receptor leads to it being constitutively expressed.

Heterozygous males develop secondary sexual characteristics with a growth spurt by age 4. Females are carriers but not affected and their male children can be.

Again this is male to male transmission so instantly exclude X linked.


What is hemochromatosis?

It is a sex limited AUTOSOMAL RECESSIVE disorder.

It is the most common single gene inherited disease in America.

Phenotype: difficulty reducing excess iron. This is more common in males (5 to 10 times more likely.
This is because women via pregnancy and menstruation have natural ways to reduce iron levels.


What is achondroplasia

An autosomal dominant disorder with incomplete dominance. Patients have a short stature, short upper and lower extremities, proportionally large head,


A mother has an unaffected father and demonstrates achondroplasia (incomplete AD). Her husband is normal. What is the risk of the child being short?

She must be heterozygous because her father is normal so must be homozygous recessive. Therefore she has a 50% chance of donating either the normal or mutant.

answer: 50% risk.


Referring to X linked diseases, there is an unaffected male and a carrier female for Hemophilia A (XLR disorder)

what is the risk that females be carriers?

Risk that males will be affected?

For the above questions, what if affected male mated with unaffected, non carrier female?

Hemophilia A is X linked recessive

1/2 of females will be carriers

1/2 of males will be affected.

X linked dominant disorders are super rare.

100% females would be obligate carriers

all males would be unaffected (inherit X from normal female.



What is unbalanced X inactivation?

It refers to how a woman carrying the X linked recessive mutation can express it because of X inactivation.

Females are somatic mosaics (tissues may have different X's inactivated.


What are the features of an X linked recessive pedigree?

No male to male transmission

The affected males far outnumber affected females.

heterozygous females are unaffected (although X inactivation)

Gene is transmitted from affected male to ALL daughters.


What is the distinguishing feature of X linked dominant pedigree?

Still no male to male transmission.

Normal female + affected male will have...

ALL Affected daughters

ALL normal sons.


What is pure somatic mosaicism and pure germ-line mosaicism?

It all depends on whether the mutation after zygote formation develops before or after the separation of germline cells from somatic cells in the embryo.

Pure somatic mosaicism: the mutation occurs in some tissues of the embryo but not the germ cells.


What is the pedigree trend for a germline mosaicism.

Parents are phenotypically normal, also test negative for being carriers, have more than one child affected with a highly penetrant AD, XLR, or XLD. (no AR because having mutations occur twice would be ridiculously improbable)


Describe the New mutation exception.

What is genetic lethal?

One out of a million chance per gamete. Affected child will share alleles with both parents.

Very rare in expressing AR diseases

The dominant mutation being expressed is so severe that persons with them don't have children so genetic lethal.


What is misattributed paternity?

The biological father is not the man named by the mother,


What is genomic imprinting?

It matters which parent you receive the gene from.

There are about 100 genes that undergo imprinting so only one of the two paternal alleles is expressed.

The specific pattern is retained in all somatic cells and will be reversed in germ cells.

Essentially, if you inherit a mutation on an imprinted gene, you have a 50% chance of being affected. It could be silenced.

Prader willi and angelman


What is the telltale sign of dominant inheritance compared to recessive on a pedigree?

What is the telltale sign of Xlinked to autosomal?

1. There is no skipping of generations in dominant inheritance. There must be skipping in recessive.

2. Autosomal: MALE to MALE transmission.

If you see no male to male transmission, then pick X linked, its the hint.


XLR disorder. Grandmother is an obligate carrier because her son is affected.

What is the chance that the mother's child will be affected when mating with a normal male?

Chance that mom is a carrier (1/2)

Punnet square: Carrier mom x normal dad = affected child p(1/4)

= 1/8

another way to think of it

carrier mom donate mutant X = 1/2

male donates Y so child is affected = 1/2

1/2 x 1/2 x 1/2 = 1/8


What is the telltale sign of germline mosaicism in a pedigree?

The disease is autosomal dominant and highly penetrant.

And MULTIPLE offspring are affected from unaffected parents.


A patient is a compound heterozygote. One mutation is not detected in either parent.

50% of the patients SNPs were maternal in origin

50% could not be matched to the dad. What does that mean?

The mother's husband is not the biological father.

50% of the patients SNPs were maternal in origin indicates that it takes recombination into consideration. You would still find 50% from father if he was biological.


How would you tell the difference between mitochondrial inheritance and X linked dominant and X linked recessive?

Mitochondrial: affected males will not pass the disease to offspring of either sex.

X linked dominant: Fathers cannot transmit to sons but daughters would be affected.

X linked recessive: An affected mother would definitely have affected sons and no affected daughters. But for mitochondrial inheritance, sons and daughters are affected from affected mother.