• Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

Card Range To Study

through

image

Play button

image

Play button

image

Progress

1/65

Click to flip

Use LEFT and RIGHT arrow keys to navigate between flashcards;

Use UP and DOWN arrow keys to flip the card;

H to show hint;

A reads text to speech;

65 Cards in this Set

  • Front
  • Back

Define: Gene

Functional unit of DNA that makes some product needed by cells (protein or RNA)

Define: Locus

The unique chromosomal location of a gene

Define: Allele

A variant form of a gene, carried at a locus on a single chromosome

Define: Genotype

The combination of alleles that a person possesses at a single locus or number of loci

Define: Phenotype

Observable characteristics of a person, organ, or cell

Define: Homozygous

Both alleles are the same at an individual locus

Define: Heterozygous

Alleles at a locus are different

Define: Hemizygous

Having only one copy of a gene or DNA sequence

Define: Monogenic

A character in which a single locus is the primary determinant; A particular genotype at a single locus is necessary and sufficient for a particular phenotype under normal circumstances

Define: Dominant Disorder/Trait

Observed in a heterozygote

Define: Recessive Disorder/Trait

Not manifested in a heterozygote

Define: Individual Single-Gene Disorders

Individual Single-Gene Disorders are rare

Explain: Principle of Uniformity

A cross between two parents differing in one trait produces progeny that appear identical to one parent

Explain: Principle of Segregation

Two copies of a gene separate from each other during gamete formation and transmission from parent to offspring

Explain: Principle of Independent Assortment

Alleles of different genes segregate into gametes independently of each other

Define: Pedigree

Graphical representation of a family tree using standard symbols

Explain: Pedigree

- Generations are labelled with Roman numerals (I,II,III) that increase from top to bottom of pedigree


- Youngest generation is at the very top


- Individuals within a generation are labelled with Arabic numerals (1,2,3) that increase from left to right

Define: Kindred

Extended family with many generations

Define: Consanguineous

Couples who are closely related due to descent from a recent common ancestor

What do these symbols represent?

What do these symbols represent?

Male


Female


Sex Unstated


Unaffected


Affected


Obligate carrier (who will not manifest disease)


Carrier who may go on to manifest disease


Deceased

What do these symbols represent?

Mating


Consanguineous mating


Siblings


Twins


Identical wins


Four children, Sex unstated


Spontaneous abortion


Termination of affected pregnancy



What are the five basic Mendelian Inheritance Patterns / Monogenic Inheritance patterns?

- Autosomal dominant


- Autosomal recessive


- X-linked dominant


- X-linked recessive


-Y-linked

What is a unique pattern of Monogenic Inheritance?

Mitochondrial DNA

Explain: Autosomal Dominant Inheritance

- Affected individuals are almost always heterozygous


- Homozygotes from rare matings between two individuals are often more severely affected or this may be lethal

What are the key features of an Autosomal Dominant pedigree?

- Affected individuals usually have an affected parent


- There are usually affected individuals in every generation


- Unaffected individuals do not transmit the disease


- Both sexes are affected and equally likely to transmit the disease

How does the most common Autosomal Dominant matings look like?

How does a rare Autosomal Dominant matings look like?





How does an Autosomal Dominant pedigree look like?



What are examples of Autosomal Dominant diseases?

- Achondroplasia


- Familial Hypercholesterolemia


- Waardenburg Syndrome Type I

Explain: Achondroplasia

- Most common cause of disproportionate small stature (Dwarfism)


- Caused by mutations in FGFR3 that cause ligand-independent activation of FGFR3


- 98% of mutations are guanine --> adenine at position 1138


- 80% of patients have a de novo mutation


- Homozygous lethal





Explain: Familial Hypercholesterolemia

- Caused by mutation in LDLR


- Results in severely elevated low-density lipoprotein (LDL) cholesterol levels and increased risk of coronary disease


- Homozygotes experience severe coronary heart disease at early age

Explain: Waardenburg Syndrome Type I

- Hearing loss, dystopia canthorum, and pigment disturbances of the iris, hair, and skin


- Cause by mutation of PAX3


- Transcription factor


- Active in neural crest cells in developing embryo


- Required for proper development of nerve tissue, craniofacial bones, and melanocytes


- Homozygotes have more severe phenotype with abnormalities of the arms



How does a Waardenburg Syndrome Type I pedigree look like?

Explain: Autosomal Recessive Inheritance

- An affected person carries two mutant alleles at the disease locus, one inherited from each parent


- Affected individuals are usually born to unaffected parents


- Parents are asymptomatic heterozygous carriers


- Affects both sexes equally

How does an Autosomal Recessive Matings look like?

Two carriers (Aa) have a 25% chance of having an affected child

Two carriers (Aa) have a 25% chance of having an affected child

Explain: Consanguinity in Autosomal Recessive Inheritance

- For disorders with unknown inheritance, parental consanguinity is a strong indication of autosomal recessive inheritance


- First-cousin marriages and matings most common


- Consanguinity produces affected individuals with identical mutant alleles due to common ancestry


- If a recessive disorder is quite frequent, carriers will be common in the population


- Two common unrelated parents may carry different mutant alleles


- Affected individual is often a compound heterozygote, rather than true homozygote

How do Autosomal Recessive pedigrees look like?



What are examples of Autosomal Recessive diseases?

- Cystic Fibrosis


- Sickle Cell Disease



Explain: Cystic Fibrosis

- Caused by mutation in CFTR which encodes a chloride channel


- Incidence ranges from 1 in 313 to 1 in 90,000 in different populations (avg. 1 in 3,200 in US)


- Dysfunction impacts many organs that secrete mucus


- Respiratory tract, pancreas, genitalia, intestine, sweat glands


- In lungs, dehydrated and viscous secretions obstructs airflow and promotes infection

Explain: Sickle Cell Disease

- Highest frequency in African Americans (1 out of 700)


- Caused by a mutation in the B subunit of hemoglobin


- Glutamic acid --> Valine at amino acid 6


- Mutation causes deoxygenated hemoglobin to form a gelatinous network of stiff polymers that distorts the RBCs


- Leads to infarctions and frequent destruction of RBCs


- Removal of RBCs exceeds production and leads to hemolytic anemia



What is an example of disease-related phenotype of carriers of an Autosomal Recessive disorder?

Sickle cell heterozygotes may exhibit sickle cell trait


- Mild anemia under normal conditions


- Extremes of physical exertion, dehydration, and/or altitude can induce disease-like symptoms and even death


- ex. Sickle cell trait associated with sudden death in competitive athletes

Explain: X-linked Inheritance



- X chromosome contains many hundreds of important genes


- Sex is an important consideration in inheritance patterns due to difference in chromosome composition


- Females: XX


- Males: XY



How does a X-linked Inheritance matings look like?



Explain: X-linked Recessive Inheritance

- Affected individuals are mostly males, usually born to unaffected parents


- Mother of an affected male is often a carrier and may have affected male relatives


- No transmission from father to son


- An affected male will transmit the disease allele to all daughters, who will be carriers but not affected


- May appear to "skip generations" due to transmission through a series of carrier females

How does an X-linked Recessive pedigree look like?



How does an X-linked Recessive pedigree with complications due to inbreeding look like?



Explain: X-linked Dominant Inheritance

- Affected individuals can be of either sex, but there are significantly more affected females than males


- No father to son transmission


- Usually at least one parent is affected


- An affected father will have affected sons but 100% of daughters will be affected


- An affected mother will transmit the mutation equally to sons and daughters


- 50% chance of an affected child

How does an X-linked Dominant pedigree look like?



Explain: X-Inactivation

- In early embryo, number of X chromosomes in each cell is determined


- If number is two (or more), all except one of the X chromosomes is inactivated


- Causes Barr body


- X inactivation occurs randomly beginning around the 8-cell stage


- Some cells inactivate paternal X, some the maternal X


- Once inactivated, same X chromosome remains inactive in all daughter cells

Define: Barr body

Inactivated X chromosome is induced to form a highly condensed chromosome which is mostly transcriptionally inactive

Compare males and females in terms of X chromosome

- Males are constitutionally hemizygous for X chromosome


- Females are functionally hemizygous for X chromosome

Define: Mosaics

Females who are heterozygous for X-linked genes

Why are females mosaics?

- Contain a mixture of genetically distinct somatic cells


- Some cells will express the normal allele, while other cells will express the mutant allele


- Pattern of X-inactivation is an important consideration for the female phenotype in X-linked disorders

What are the impacts of X-Inactivation?

- Females heterozygous for an X-linked Recessive Disorder may be manifesting heterozygotes


- Females heterozygous for an X-linked Dominant Disorder tend to have milder and more variable phenotypes than affected males

Explain why females heterozygous for an X-linked Recessive Disorder may be manifesting heterozygotes

- "Bad Luck" of being affected by the disease, despite being heterozygous for a recessive trait


- Occurs when most cells in a tissue critically important in disease development have inactivated the X with the normal allele

Explain why females heterozygous for an X-linked Dominant Disorder tend to have milder and more variable phenotypes than affected males

- The mutant allele is located on an inactivated X in at least a proportion of their cells


- Some X-linked dominant disorders are lethal in male, but the milder phenotype in females allows them to survive and even reproduce

How does an X-linked Dominant and Male Lethality pedigree look like?



What happens to Mosaic females if the phenotype depends on a circulating product?

- Mosaic females are usually clinically unaffected


- Averaging effect of normal and abnormal cells


- Ex. Hemophilia A (X-linked recessive)

Explain: Hemophilia A

- Phenotype depends on a circulating product


- Mosaic females are usually clinically unaffected


- X-linked Recessive


- Caused by mutation in Factor 8 gene, which is a required component of blood clotting cascade


- Results in severe and prolonged bleeding

What happens to Mosaic females if the phenotype is localized to a certain type of cell

- Mosaic females may exhibit patches of normal and abnormal tissue


- Ex. Hypohidrotic Ectodermal Dysplasia (X-linked recessive)

Explain: Hypohidrotic Ectodermal Dysplasia

- Phenotype is localized to a certain type of cell


- Mosaic females may exhibit patches of normal and abnormal tissue


- X-linked Recessive


- Caused by mutations in extodysplasin A, which is required for interaction in early embryo


- Results in absence of sweat glands, sparse hair, and missing/abnormal teeth

What happens to Mosaic, heterozygous females?

- Mosaic, heterozygous females may exhibit Skewed X-Inactivation


- May occur due to chance alone (unbalanced random inactivation)


- May also occur due to a proliferative or survival advantage in cells that inactivate one X chromosome







What happens to Mosaic females with X chromosome carrying the mutation?

- Mosaic females with X chromosome carrying the mutation, may be preferentially inactivated in critical cells or tissues


- Ex. Bruton agammaglobulinemia (X-linked recessive)

Explain: Bruton agammaglobulinemia

- Mosaic females with X chromosome carrying the mutation, may be preferentially inactivated in critical cells or tissues


- X-linked Recessive


- Caused by a mutation in Bruton's tyrosine kinase (Btk) gene that leads to a severe block in B cell development


- Males lack mature B cells and require a lifelong infusion of human antibodies


- Females have B cells, all of which have mutant X inactivated



Why would a normal X chromosome may be preferentially inactivated in Mosaic females?

In some cases for Mosaic females, the normal X may be preferentially inactivated due to an X-autosome translocation on the mutant chromosome