Genetics Flashcards
Each gene contains the genetic information required to produce a _____. Each of these is made specifically to perform a necessary body function
protein
Mutation of a gene locus affecting only one chromosome? Both chromosomes?
heterozygous for the disorder
homozygous for the disorder
Permanent change in DNA
mutation
Mutation affecting germ cells can….
be transmitted to progeny aka is inherited
Mutations affecting somatic cells can…
form tumors or developmental malformations
3 types of mutations
point mutation (missense mutation)
frameshift mutation
Trinucleotide repeat mutations
Describe Point mutations and give example
single nucleotide base substitued
i.e sickle cell anemia
Describe frameshift mutation
when one or two base pairs are inserted or deleted causing an alteration in the reading frame of the DNA strand
Describe trinucleotide repeat mutation and give an example
Amplification of sequence of 3 nucleotides
i,e- Fragile X syndrome - a normal human has 5-54 repeats of CGG, while a person with Fragile X syndrome has 230-4000
3 examples of alterations in protein-coding genes other than mutations
- Polymorphisms - single nucleotide polymorphism and copy number variations
- Epigenetic changes
- Alterations in non-coding RNAs
Describe single nucleotide polymorphism and give examples of what this could be a marker of:
variation in just one nucleotide at a single site on the DNA molecule.
May be markers for diabetes or hypertension
What is the difference between single nucleotide polymorphism and point mutation
the frequency.
Missense/point mutations dont occur often
Single nucleotide polymorphism occurs VERY ofter
How many single nucleotide polymorphisms have been identified and where do most occur
Over 6,000,000 have been identified, but most are within exons, introns, or intergenic regions
Describe copy number variations and what does this account for….
When you have different numbers of large continuous stretches of DNA, from 1,000 to millions of base pairs.
This may account for phenotypic variation
What is an epigenetic change?
when a modulation of gene expression occurs without an altered DNA sequence
ie. a methylation of promoter regions makes them inaccessible to RNA polymerase causing reduction in protein synthesis
Describe alterations in non-coding RNAs
micro-RNAs inhibit translation of their target messenger RNAs into their corresponding proteins
T or F; Autosomal dominant disorders create outward physical changes and many exhibit a delayed age of onset even though the mutant gene has been there since birth
true
2 examples of autosomal dominant disorders
Huntington disease
Neurofibromatosis (from lecture) - seen nearly 100% of the time but the extent is variable - some people have tumors everywhere on their body
Define reduced or incomplete penetrance
person has a mutant gene but does not express it phenotypically
define variable expressitivity and what autosomal dominant disorder is an example of this
trait is seen phenotypically in the individuals having the mutant gene but is expressed differently among individuals
Define: de novo mutation
affected individuals may not have affected parents because their disease arose from a new mutation
What represents the largest group of mendelian disorders?
autosomal recessive
In autosomal recessive disorders, if the mutant gene is rare, there is a strong probability that the affected child (proband) is the product of a _________________
consanguineous relationship (coming from the same descendants)
In autosomal recessive disorders, the age of onset is more frequent at what period in life?
and
describe the expression of the defect
early in life
and
defect tends to be more uniform and complete penetrance is common
What is the one Y-linked disorder?
hairy ears
Almost all x-linked disorders are: recessive or dominant?
recessive
Who is affected by x-linked disorders?
females who are homozygous for the disorder (unless they have an unusual x-linked dominant disorder) and all males because they only have one x-chromosome
what would be the reason a heterozygous woman may demonstrate full expression even though the x-linked disorder is recessive?
unfavorable lyonization (inactivation of an abnormally high percentage of normal X chromosomes leading to clinically evident heterozygote disease)
Describe lyonization
- occurs only in females
- 16 days after conception, all but one X chromosome is randomly inactivacted in all of the cells of the zygote
- either the maternal or paternal X may be inactivated in each cell and that X remains inactivated for life
Example of X-linked dominant
Oral-Facial-Digital syndrome (OFD) type I
Diseases caused by mutations in STUCTURAL PROTEINS
Marfan syndrome
Ehlers-Danlos Syndromes
How does Marfan Syndrome:
- occur - give general characteristics of people who tend to get this - prevalence - symptoms people with syndrome get
Autosomal dominant disorder of CT due to mutation of “FBN1 gene” –> you get abnormal “fibrillin” (which is a glycoprotein necessary for normal elastic fiber production
1 in 5000
Tall, thin body with abnormally long legs, arms, and fingers (Wolters….)
Dislocation of the eyes
Aortic aneurysm and dissection leading to heart failure and aortic rupture
How does Ehlers-Danlos syndrome come about?
Symptoms of people who get it?
collagen synthesis problem
- hyperextensible skin and hypermobile joints (can extend fingers all the way back)
- Skin fragility and delayed wound healing
- rupture of colon, large arteries
- hernias
Diseases caused by mutations in RECEPTOR POINTS
Familial Hypercholesterolemia Cystic Fibrosis (lecture)
Frequency of hypercholesterolemia?
Where is the mutation?
What can this cause?
One of the most common inherited disorders:
1 in 500
Mutation in the gene for the LDL receptor resulting in impaired metabolism and increased LDL cholesterol in plasma
This causes:
xanthomas of the skin
premature atherosclerosis - plaque build-up in arteries
In hypercholesterolemia, how much more cholesterol do homozygotes and heterozygotes have compared to the normal levels?
homozygous - 5X
-often die of MI before age of 20
heterozygous - 2-3X
In hypercholesterolemia, understanding the role of LDL receptors have led to the design of what medication?
And what does this medication control?
the statin family of drugs
-they control cholesterol levels
Diseases caused by mutations in ENZYME PROTEINS
Phenylketonuria
and
Lysosomal Storage Diseases Tay-Sachs disease Niemann-Pick disease Gaucher disease Mucopolysaccharidoses
Phenylketonuria:
- Type of disorder: dominant or recessive?
- prevalence and whose affected?
- lack of what enzyme? and what does this lead to?
- when does onset occur?
- how can this be treated if detected early on?
- autosomal recessive disorder
- 1 in 10,000 white infants
- lack of phenylalanine hydroxylase, leading to hyperphenylalaininemia and PKU
- normal at birth, but within 6 months elevated phenylalanine levels impair brain development and mental retardation is evident
- Screening at birth is mandatory in USA and restricting dietary phenylalanine intake will prevent mental retardation
Lysosomal Storage Diseases
- Type of disorder: dominant or recessive?
- Whose affected?
- How does this occur?
- Symptoms of a person withthis?
- Autosomal recessive transmission
- infants and young children
- accumulation of insoluble large molecules in macrophanges with hepatosplenomegaly
- frequent CNS involvement, mental retardation, and/or early death
what is it called if two or more genes, plus environmental/nongenetic influences, are responsible for a disorder?
give an example
multifactorial inheritance
ie- genes make one susceptible for diabetes and obesity is the environmental factor contributing as well
What is the composite picture of the human chromosome strands that are stained, photographed, and arranged in pairs?
karyotype
In as many as 50% of 1st trimester spontaneous abortions, the fetus has a ________
chromosomal abnormality
Euploid is
a normal chromosomal count (2 x 23 = 46)
Polyploidy is
an increased chromosomal count that is a multiple of that normally seen (3 x 23 or 4 x 23)
results in spontaneous abortion
Aneuploidy and examples of it
any number that is not an exact multiple of the normal chromosome count
examples include:
an extra chromosome (trisomy = 2 X 23 + 1 = 47)
an absence of a chromosome (monosomy 2 X 23 -1 = 45)
Translocation is…
the transfer of a part of one chromosome to another nonhomologous chromosome
Trisomy 21 aka Down Syndrome:
- Is it common within chromosomal disorders?
- What is associated with this occuring?
- Symptoms of child with this syndrome?
-Most common of the chromosomal disorders
-associated with increased maternal age
45 years old - 1:25
-mental retardation, epicanthic folds (skinfold of upper eyelid covering inner angle of eye), flat facial profile, increased susceptibility to infection (severe periodontal disease in childhood), large tongue, cardiac malformations
-How does Trisomy 21 occur?
-this occurs due to meiotic non-disjunction of chromosome 21 during formation of the ovum
Klinefelter Syndrome:
- What is the mutation
- Characteristics/symptoms
- Dental fact
defined as male hypogonadism that develops when there are two X chromosomes and one or more Y chromosomes
- increased length of lower limbs, reduced body hair, gynecomastia - most common reason for hypogonadism (swelling of breasts in males)
- increased frequency of taurodontism (body of tooth and pulp chamber is enlarged vertically at the expense of the roots)
Turner Syndrome
- What is the mutation - Symptoms of people with this
due to partial or complete absence of the X chromosomes
-short stature, webbed neck, low post hairline, high-arched palate. primary amenorrhea (absence of menstruation)
Diagnosis of Genetic diseases
- fluorescence in situ hybridization
- comparative genomic hybridization
- molecular diagnosis of genetic disorders
How is fluorescence in situ hybridization achieved?
used fliorescent dye-labeled probes that recognize sequences specific to chromosomal regions
How is comparative genomic hybridization achieved?
uses different colored dyes attached to large segments of the test DNA and normal DNA, followed by hybridization
How is molecular diagnosis of genetic disorders achieved?
- PCR analysis - amplify the DNA in question
- compare the order of nucleotides of this DNA to a normal DNA sequence
- use restriction enzymes and run the segments on gel electrophoresis, compare to normal DNA
Prenatal Indications for genetic analysis
- mother’s age > 34 years
- parent who is a carrier of a chromosomal translocation
- history of a previous child with chromosomal abnormality
- parent who is a carrier of an x-linked disorder
Postnatal indication for genetic analysis
- multiple congenital abnormalities
- unexplained mental retardation and/or delayed development
- suspected aneuploidy (ie - down syndrome)
- suspected sex chromosomal abnormality
- infertility
- multiple spontaneous abortions
