Lecture 12 - Genetic Diseases Flashcards
What are the basic units of the body?
Cells
Where are chromosomes located in the cell?
in the nucleus
genes reside on what?
chromosomes
Genes carry the code for _____
proteins
the genetic code consists of 4 letters, what are the letters and names?
Adenine
Cytosine
Guanine
Thymine
the nucleus of each human cell contains strands of DNA known as __________ and they are arranged in _____
chromosomes and they are arranged in pairs
There are 22 pairs of ____ chromosomes and one pair of ____ chromosomes
22 pairs of autosomal chromosomes and one pair of sex chromosome
Each chromosome consists of a series of genes, and the Human Genome Project has identified about how many protein-coding genes?
19,000
Each gene contains the genetic information required to produce a ____.
protein
Each ____ is made specifically to perform a necessary body function
protein
Mutations of a certain gene locus may affect one or both of the ______ in a pair
chromosomes
What does it mean to be heterozygous for a disorder?
when one chromosome in the pair is affected
what does it mean to be homozygous for a disorder?
if both chromosomes at a given gene locus are affected
what is the definition of mutation>
permanent change in the DNA
when a mutation affects germ cells, it can be transmitted to _____
progeny
when a mutation affects a somatic cell it can result in what two things?
tumors or developmental malformations
What are the names of the three types of mutations?
point (missence) mutation
frameshift mutation
trinucleotide repeat mutation
what is the definitions of a point (missence) mutation and what is an example?
single nucleotide base substituted
Examp: sickle cell anemia
What is the definition of a frameshift mutation?
insertion or deletion of one or two base pairs, altering reading frame of the DNA strand
what is the definition and what is an example of trinucleotide repeat mutation?
amplification of sequence of 3 nucleotides
Examp: Fragile X syndrome
what is a single nucleotide polymorphism?
variation in just one nucleotide (for example, A or T) at a single site on the DNA molecule
over 6 million polymorphisms have been identified, but most are within which three regions?
exons
introns
and intergenic regions
polymorphisms may be markers for multigenic complex diseases, such as what?
diabetes or hypertension
what are different numbers of large contiguous stretches of DNA, from 1,000 to million of base pairs?
copy number variations
in copy number variations how many involve gene-coding sequences, and this may account for variation in what?
half involve gene-coding sequences, and it may account for much PHENOTYPIC variation
what refers to modulation of gene expression without altered DNA sequence?
epigenetic changes
epigenetic changes are important in what?
development as well as normal homeostasis
with epigenetic changes, methylation of promoter regions makes them inaccessible to RNA polymerase, thus reducing what?
protein synthesis
what is the definition of alterations in non-coding RNAs?
micro-RNAs (miRNA’s) inhibit translation of their target messenger RNAs into their corresponding proteins
mendelian disorders are diseases caused by what?
single gene defects
what is the definition of autosomal dominant disorders?
implies that the altered gene locus is on an autosome and disease will be evident clinically when only one of the chromosomes i the pair exhibit a mutation at the affected gene locus
the majority of autosomal dominant disorders create which type of changes?
outward physical changes
when is the mutant gene present in autosomal dominant disorders and what is an example?
it is present from birth
example: Huntington disease
(T/F)
- Many Autosomal dominant disorders are exhibited at birth
- In autosomal dominant disorders the mutant gene is present from birth.
- False - many autosomal dominant disorders exhibits a delayed age of onset
- True
With autosomal dominant disorders, how many parents are usually affected?
one of he parents is usually affected
(T/F) only females can have the disorder and transmit the mutant gene
False - both males and females can have he disorder and transmit the mutant gene
what percent of the offspring will have the disease if only one parent is affected with autosomal dominant diseases?
half or 50% of the offspring will have the disease
what is the definition of reduced or incomplete penetrance?
person has a mutant gene but does not express it phenotypically
what is the definition of variable expressivity?
trait is seen phenotypically in the individuals having the mutant gene but is EXPRESSED DIFFERENTLY among individuals
what is the definition of de novo mutation?
affected individuals may not have affected parents because their disease arose from a new mutation
what is the definition of autosomal recessive disorders?
recessive implies that the trait is expressed only if both genes at a given locus are affected (homozygous individuals)
what is the largest group of mendelian disorder?
autosomal recessive disorders
with autosomal recessive disorders do the parents of the affected individual show the disease?
the parents of the affected individual usually do not show the disease
offspring of heterozygous carrier parents have what chance of getting the disease
offspring of heterozygous carrier parents have a one in four chance of the disease
offspring of heterozygous carrier parent have what chance of being a carrier?
one and two chance of being a carried
if the mutant gene is rare, there is a strong probability that the affected child (proband) is the product of what kind of relationship?
consanguineous
this means - relating to or denoting people descended from the same ancestor.
what are the basic concepts of autosomal recessive disorders?
- two germline mutations (one from each parent)
- equally transmitted by men and women
- 25% of offspring; horizontal pattern in family
what type of pattern is seen in families with autosomal recessive disorders?
horizontal pattern in family
with autosomal recessive disorders - many of these disorders present with enzyme defects that produce what?
inborn error of metabolism
in heterozygous individuals with autosomal recessive disorders, the disease is not clinically event but they may possess reduced amount of what?
the normal enzyme
carriers are heterozygous individuals (the disease is not evident clinically)
in autosomal recessive disorders the age of onset is more frequently when?
in early life
the expression of the defect tends to be more ____ and _____ _____ is common
tends to be more uniform and complete penetrance is common
although new mutations do occur, they are usually not detected for what reasons?
since that individual would be a carrier without clinical manifestations
almost all X-linked disorders are recessive or dominant?
recessive
are males or females carried for X linked disorders?
females - because they are usually heterozygous for the gene because they have 2 X chromosomes
who is affected by x linked recessive disorders?
homozygous females and males (who are automatically hemizygous because they have only 1 X chromosome) are affected
- mutant genes are on the X (sex) chromosome
- women must inherit 2 mutated copies to be affected
- all men who inherit the mutation are affected (only one X chromosome)
although it is rare, heterozygous females may demonstrate full expression due to what?
unfavorable lyonization
what is lyonization?
- 16 days after concpetion, all but one X chromosome is randomly inactivated in all of the cells within the zygote’’- Either the maternal or paternal X may be inactivated in each cell and that X remains inactivated in the progeny of the cell
with lyonization, the cells in normal females represent a mixture of two cell types, what are they?
those with active paternal X and those with active maternal X
- in disorders of the X chromosome, typically females are an even mixture of normal and abnormal chromosomes
what is unfavorable lyonization?
inactivation of an abnormally high percentage of normal X chromosomes, leading to clinical evidence of the disease in a heterozygote
what is affected in x linked dominant and what is an example?
heterozygous
homozygous
hemizygous are all affected
Example: Oral-Facial-Digital syndrome (OFD) type I
What are 2 diseases that are caused by mutations in structural proteins?
Marfan syndrome
Ehlers-Danlos Syndrome
what is Marfan syndrome?
-Autosomal dominant disorder of connective tissue due to mutation of the FBN1 gene, resulting in abnormal FIBRILLIN, a glycoprotein necessary for normal elastic fiber production
what is the prevalence of Marfan syndrome?
1 in 5,000
what are some clinical manifestations of Marfan syndrome?
tall, thin body habitus with abnormally long legs, arms and fingers (arachnodactyly - spider fingers)
-Dislocation of lens of the eye
-Aortic aneurysm and dissection leading to heart failure and aortic rupture
Examples: Abraham lincoln? sudden death of basketabll players?
