Genetic diseases Flashcards by asw asw

Mutations of a certain gene _____ may affect one or both of the chromosomes in a pair

locus

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_________ refers to a permanent change in the DNA

Mutation

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mutations affecting __________ cells can result in tumors or developmental malformations

somatic cells

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what is a Point mutations (missense mutation)? what is an example of a point mutation?

single nucleotide base substituted.

Example: sickle cell anemia

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what is a Frameshift mutation?

insertion or deletion of one or two base pairs, altering reading frame of the DNA strand

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what occurs during Trinucleotide repeat mutations?

amplification of sequence of 3 nucleotides

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what is an example of trinucleotide repeat mutations?

Fragile X syndrome

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permanent genetic changes affecting ________ can be inherited

germ cells

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what are the 3 types of mendelian disorders?

Autosomal Dominant
Autosomal Recessive
Sex-linked (X-linked) Disorders

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what are the 2 types of polymorphisms?

Single nucleotide polymorphisms

Copy number variations

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a _________ is a variation in just one nucleotide (for example, A or T) at a single site on the DNA molecule

single nucleotide polymorphism

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single nucleotide polymorphisms May be markers for multigenic complex diseases, such as _______ or __________

diabetes or hypertension

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what are the characteristics of Copy number variation polymorphisms?

different numbers of large contiguous stretches of DNA, from 1,000 to millions of base pairs
About half involve gene-coding sequences

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______________ changes result in modulation of gene expression without altered DNA sequence

epigenetic changes

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_________ of promoter regions in the DNA makes them inaccessible to RNA polymerase

Methylation

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what type of residues are methylated during epigenetic inactivation?

cytosine

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_______________ inhibit translation of their target messenger RNAs into their corresponding proteins

Micro-RNAs (miRNA’s)

“functions in RNA silencing and post-transcriptional regulation of gene expression”

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Autosomal dominant implies that the altered gene locus is on an _________

autosome

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during what type of disorder will the disease be evident clinically when only ONE of the chromosomes in the pair exhibits a mutation at the affected gene locus

autosomal dominant

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T/F: The majority of autosomal dominant disorders create outward physical changes

true

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huntington’s disease is classified as a ___________ disorder

autosomal dominant

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T/F: Approximately one-quarter of the offspring will have the disease if only one parent is affected with huntington’s disease

FALSE

one half of offspring

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what is “reduced or incomplete penetrance”?

Person has a mutant gene but does not express it phenotypically

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_____________ means the trait is seen phenotypically in the individuals having the mutant gene but is expressed differently among individuals

variable expressivity

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how could a child suffer from an autosomal dominant disorder, but their parents are unaffected?

due to "De Novo mutation" - the parents don't have the autosomal dominant gene because their disease arose from a new mutation

_________ disorders represent the largest group of mendelian disorders

autosomal recessive disorders

T/F: the parents of people suffering from autosomal recessive disorders usually show similar symptoms as their offspring

FALSE parents are usually asymptomatic

when are rare autosomal recessive diseases usually seen?

when the affected child (proband) is the product of a consanguineous relationship (INCEST Y'ALL)

what are the characteristics of all autosomal recessive disorders?

• Two germline mutations (one from each parent) to develop disease * Equally transmitted by men and women * 25% of offspring; horizontal pattern in family

Many autosomal recessive disorders present with _______ defects that produce inborn errors of metabolism

enzyme

_________ individuals of autosomal recessive disorders will often show reduced, but not complete mutation/inactivity, of the normal enzyme

heterozygous individuals AKA "carriers"

X-linked disorders are also known as "_________" disorders

sex-linked

T/F: although rare, Y-linked genetic disorders do occur

FALSE - nobody has ever found a y-linked disorder (thanks dad)

what is the only trait that has been linked to the y-chromosome?

hairy ears

Almost all X-linked disorders are __________ in their inheritance pattern

recessive

what inheritance pattern is observed during sex-linked disorders (heterozygosity, homozygosity, et cetera

- women must be homozygous to show disease | - men are heterozygous (mutated X is from the MOTHER)

what occurs during lysonization?

- occurs Sixteen days after conception | - all but ONE X chromosome is randomly inactivated in all of the cells within the zygote

what is Unfavorable lyonization?

refers to inactivation of an abnormally high percentage of normal X chromosomes

the result of ___________ would be the presence of x-linked disorders appearing in heterozygous females

unfavorable lysonization

Oral-Facial-Digital syndrome (OFD) type 1 is an example of what type of genetic disease?

x-linked DOMINANT

Marfan syndrome is a autosomal dominant disorder of _________________

connective tissue

what gene is mutated in Marfan syndrome?

the FBN1 gene

a mutation of the FBN1 gene (marfan syndrome) will result in abnormal formation of what connective tissue protein?

fibrillin

what is the prevalence of marfan syndrome?

1 in 5,000

what are the physical characteristics of someone suffering from Marfan syndrome?

- Tall, thin body habitus with abnormally long legs, arms and fingers - Dislocation of lens of the eye - Aortic aneurysm and dissection leading to heart failure

At least ___ different types of ehler-danlos syndrome may exist

what are the characteristics of Ehlers-Danlos syndrome?

Hyperextensible skin and hypermobile joints Skin fragility and delayed wound healing Rupture of colon, large arteries Hernias

what is the prevalence of Familial Hypercholesterolemia?

1 in 500

Familial Hypercholesterolemia result in the mutation of what type of proteins?

LDL receptors

what is the result of Familial Hypercholesterolemia?

- impaired metabolism and increased LDL cholesterol in the plasma - causes xanthomas of the skin and premature atherosclerosis

what are the effects on cholesterol for heterozygotes and homozygotes during Familial Hypocholesterolemia?

Heterozygotes have 2-3x increased cholesterol levels homozygotes have over 5x normal levels

what are the 2 diseases caused by Mutations in Structural Proteins? (which 2 impair normal collagen synthesis/function)

1) Marfan Syndrome | 2) Ehlers-Danlos Syndromes

__________________ results from the mutation of a receptor protein

Familial Hypercholesterolemia

what 2 diseases are caused by by Mutations in genes coding for Enzyme Proteins?

1) Phenylketonuria | 2) Lysosomal Storage Diseases

____________ is an autosomal recessive disorder that affects 1 in 10,000 Caucasian infants

phenylketonuria

what enzyme is lacking during phenylketonuria? what does this cause?

- phenylalanine hydroxylase | - leads to hyperphenylalaninemia and PKU

elevated phenylalanine will have what effects on infants?

- elevated phenylalanine levels impair brain development | - leads to mental retardation

what are the characteristics of lysosomal storage diseases?

- Autosomal recessive transmission - Commonly affect infants and young children - Accumulation of insoluble large molecules (sphingolipids and mucopolysaccharides) in macrophages

what are some examples of lysosomal storage diseases?

Tay-Sachs disease Niemann-Pick disease Gaucher disease Mucopolysaccharidoses (Hurler & hunter disease)

Disorders with Multifactorial Inheritance share what common characteristics?

- Two or more genes responsible, plus environmental, nongenetic influences - Frequency of inheritance ranges from 2-7%

what causes Mucopolysaccharide storage diseases?

Due to lack of any one of several enzymes necessary to degrade mucopolysaccharides

what are the physical signs of mucopolysaccharide storage diseases?

Affected patients have: - coarse facial features - clouding of cornea - joint stiffness - mental retardation

________ disease is caused by a deficiency of alpha-L-iduronidase

Hurler Disease

what therapy can help patients with Hurler disease?

bone marrow transplants enzyme treatments

Hunter Syndrome is the result of a deficiency of ___________

L-iduronate sulfatase | hurler is ALPHA-L-iduronidase

what is the inheritance pattern of Hunter syndrome?

X-linked inheritance pattern

how does Hunter syndrome differ from Hurler syndrome?

hunter syndrome shows an absence of corneal clouding and milder clinical course

it is estimated that 1 in 200 newborns have a ______________ abnormality

chromosomal abnormality

A normal chromosomal count (2 X 23 = 46) is termed _______

euploid

An increased chromosome count that is a multiple of that normally seen (i.e. 3 X 23 or 4 X 23) is termed ___________

polyploidy

what happens to most cases of polyploidy?

spontaneous abortion

Any chromosome number that is not an exact multiple of the normal chromosome count is termed _________

aneuploidy

_____________ and __________ are both examples of aneuploidy

trisomy (extra chromosome) and monosomy (lacking 1 chromosome)

________________ is the transfer of a part of one chromosome to another nonhomologous chromosome.

Translocation

__________ is when a chromosome breaks in two points, then the released fragment is reunited after a complete turnaround

Inversion

what causes down syndrome?

a trisomy (3rd copy) of the 21st chromosome

what factor plays the greatest role in the likelihood of down syndrome?

advanced maternal age

________________ of chromosome 21 during formation of the ovum is the cause of down syndrome

meiotic non-disjunction of chromosome 21

what are the 2 Cytogenetic Disorders Involving Sex Chromosomes?

1) Klinefelter Syndrome 2) Turner Syndrome ***down's syndrome is NOT on the sex chromosome

____________ is Defined as male hypogonadism that develops when there are at least two X chromosomes and one or more Y chromosomes

Klinefelter Syndrome

what causes Turners syndrome?

Due to partial or complete absence of one of the X | chromosomes

what are the symptoms of turners syndrome?

``` Markedly short stature webbing of the neck low posterior hairline shield-like chest high-arched palate variety of congenital cardiovascular malformations failure to develop secondary sex characteristics primary amenorrhea ```

what techniques can be used to diagnose genetic diseases?

1) Fluorescence in situ Hybridization (FISH) 2) Comparative Genomic Hybridization 3) molecular diagnosis (PCR amplification)

what are the indications for PRENATAL genetic testing?

Mother’s age >34 years Parent who is a carrier of a chromosomal translocation Hx of a previous child with chromosomal abnormality Parent who is a carrier of an X-linked disorder

what are the indications for POSTNATAL genetic testing?

Multiple congenital anomalies Unexplained mental retardation and/or developmental delay Suspected aneuploidy (e.g., Down syndrome) Suspected sex chromosomal abnormality Infertility Multiple spontaneous abortions

what is an autosomal dominant disease that has nearly 100% penetrance, but has extreme variability in its expression?

neofibromatosis

"Hemophilia A" is an example of what class of inherited disorder?

x-linked

what genetic disorder will commonly cause an enlarged tongue?

Down syndrome

_______________ (a sex chromosome disorder) will increased the frequency of taurodontism

Klinefelter Syndrome

most people with ________________ will have a genotype of 47,XXY

Klinefelter Syndrome

what is the genotype for people with Turners syndrome?

45,X