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Flashcards in Genetic Disease Deck (50)
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1
Q

What does alteration in the genetic code cause?

A

Mutations

2
Q

How does permanent damage in the DNA affecting germ cells come to be?

A

Can be inherited

3
Q

What does Permanent DNA damage in Somatic cells cause?

A

May result in tumor or developmental abnormality

4
Q

__________ is a a single base substitution.

A

Point mutation

5
Q

_______ is an insertion or deletion of 1-2 base pairs.

A

Frameshift

6
Q

____ is an amplification of a 3-nucleotide sequence.

A

Trinucleotide repeat

7
Q

What other 3 factors can impact protein coding Gene function?

A
  1. Polymorphisms
  2. Epigenetic changes
  3. Alterations in Non-coding RNA’s
8
Q

What are the types of Genetic disorders?

A
  • Mendelian Disorders
  • Autosomal Dominant
  • Autosomal Recessive
  • Sex-linked (x-linked) disorders
  • Disorders with multifactorial (polygenic inheritance)
  • Cytogeneic Disorders (chromosomal aberrations) (autosomes and Sex chromosomes)
9
Q

Tell me about autosomal dominant disorders….

A
  • Mutated gene on ONE of the autosomes
  • Expressed in heterozygous state, one parent usually affected.
  • Often present with outward physical changes, but these may have delayed age of onset (Huntingtons disease)
10
Q

What is reduced or incomplete Penetrance?

A

An autosomal dominant occurrence where a person has a mutant gene but either doesn’t, or only partially expresses it phenotypically.

11
Q

What is Variable expressivity?

A

If the expression can be identified in all affected persons but to differing extents.

12
Q

What is New or De novo mutation?

A

If neither parent is affected/no family history.

13
Q

_______ is an Autosomal disease with nearly 1000% penetrance yet variable expressivity.

A

Neurofibromatosis (Bumps all over face)

14
Q

Which is the larges group of Medelian disorders?

A

Autosomal Recessive

15
Q

Tell me about Autosomal recessive disorders…

A
  • Affect patients are homosygous; Parents appear unaffected.
  • 25% of offspring are affected; 50% of offspring are carriers
  • If the Recessive gene is rare in the population, disorder may be the result of consanguinity.
16
Q

Many AR conditions are _________ defects leading to ______.

A

Enzyme defects leading to Metabolic dysfunction.
* Heterozygous patients are unaffected clinically as they typically have reduced but still adequate levels of the normal functional enzyme.

17
Q

When is age of onset with AR disorders?

A

Early, complete penetrance is also common

18
Q

Tell me about X-linked Disorders….

A
  • all are not the X Chromosome
  • Most are recessive
  • Females having two x chromosomes are usually unaffected heterosygous carriers
  • Males being hemizygous, will express the disorder.
  • Y chromosome only carries one significant gene SRY (sex determining region)
19
Q

What is an example of x-linked disorder?

A

Hemophilia A

20
Q

What is lyonization?

A

16 days post conception most of one X chromosome in the female zygote is inactivated randomly resulting in the formation of a Barr Body in each cell.
*All progeny of that cell will carry the same inactivated X chromosome

21
Q

What are the Diseases caused by Mutations in Structural proteins?

A
  • Marfan Syndrome

- Ehlers-danlos syndromes

22
Q

Tell me about Marfan Syndrome….

A
  • Autosomal dominant
  • Prevalence 1 in 5000
  • Mutation of FBN1 gene resulting in abnormal fibrin, a glycoprotein necessary for normal elastic fiber production.
23
Q

What are the characteristics of Marfan Syndrome?

A
  • Tall thin body
  • Abnormally long legs
  • Arachnodactyly
  • dislocation of lens of eye
  • aortic aneurysm and dissection leading to heart failure and aortic rupture.
24
Q

Tell me about Ehlers-Danlos Syndromes..

A
  • At least 6 clinical variants of disease
  • Problem with collagen synthesis, among 30 distinct types of collagen.
  • Variable tissue distribution of these collagens may explain clinical heterogeneity of EDS’s
25
Q

What are some examples of Diseases caused by mutations in Gene Encoding Receptor proteins or Channels?

A
  • Familial Hypercholesterolemia (LDL receptor)

- Cystic fibrosis (Chloride channel protein)

26
Q

Tell me about Familial Hypercholesterolemia..

A
  • Its one of the more common inherited disorders (autosomal dominant)
  • Frequency 1 in 500
  • Mutation of the gene that encodes the LDL receptor
  • Results in impaired metabolism and increased LDL cholesterol in the plasma
27
Q

What are manifestations of Familial Hypercholesterolemia?

A
  • Multiple xanthomas of the skin
  • Premature atherosclerosis
  • Heterozygotes = 2-3x increased LDL
  • Homozygotes = over 5x increased LDL
  • Homozygotes often die of MI before age 20
  • Lomitapide used to treat homozygous form.
28
Q

What are the diseases caused by mutations in Enzyme Proteins?

A

Phenylketouria
Galactosemia
Lysosomal storage diseases

29
Q

Tell me about Phenylketonuria….

A
  • AR disorder
  • 1:10,000 White infants
  • lack of phenylalanine hydroxylase
  • Leads to hyperphenylalaninemia and PKU
  • Affected infants are normal at birth but increased phenylalanine levels impair brain development = mental retardation by 6 months of age. (restricting dietary sources of Phenylalanine will prevent retardation in these individuals thus screening is mandatory in US.
30
Q

What are Storage diseases?

A

Autosomal recessive transmission that commonly affects infants and young adults = accumulations of large insoluble molecules in macrophages leads to hepatosplenomegaly.
*Frequent CNS involvement leads to neuronal damage, mental retardation and or early death.

31
Q

What are the 4 lysososomal storage diseases?

A
  • Tay-sachs disease
  • Niemann-pick disease
  • Gaucher disease
  • Mucopolysaccharideoses
32
Q

Tell me about Mucopolysaccharide storage diseases….

A

Most are Ar

  • Due to lack of any one of several enzymes necessary to degrade mucopolysaccahrides
  • affected patients often have coarse facial features, coding of cornea, joint stiffness and mental retardation.
33
Q

Tell me abut Hurler Disease (MPS type 1)?

A

AR disease caused by deficiency of alpha-L-iduronidase.

  • Life expectancy 6-10 years
  • Bone marrow transplant may improve outlook but cost 300K a year.
34
Q

What is Hunter Syndrome?

A

A chronic X-linked intolerance to sitting in lecture from late september through late november…….okay it is x-linked but is due to a deficiency in L-iduronate sulfates and is similar to Hurler disease without the corneal clouding.

35
Q

What are Multifactorial disorders?

A

2 or more genes responsible plus environmental influences:

  • BP
  • Hair color
  • Height and weight
36
Q

What is normal chromosome count?

A

46

37
Q

1 in _____ newborns has a chromosomal abnormality.

A

200 *Thought to contribute to 50% of 1st trimester spontaneous abortions.

38
Q

what is a Euploid?

A

a normal chromosome count (46)

39
Q

What is a Polyploidy?

A

an increased chromosome count that generally results in spontaneous abortion.

40
Q

Euploid, polyploidy, monosomy, trisomy aneuploidy are both examples of ______.

A

Numeric Autosomal aberrations

41
Q

What is monosomy?

A

Missing chromosome

42
Q

What is Trisomy?

A

Extra chromosome

43
Q

What is aneuploidy?

A

any number that is not an east multiple of the normal chromosome count.

44
Q

What are some examples of Structural Autosomal Aberrations?

A

Translocations = transfer of a part of one chromosome to another nonhomologus chromosome. *reciprocal translocation is where fragments are exchanged between two chromosomes.

Deletion = loss of a portion of a chromosome

Inversion = chromosome breaks in two point, then released fragment is reunited after a complete turnaround.

45
Q

What are cytogenetic disorders involving autosomes?

A
Trisomy 21 (down syndrome) = most common one.
- Due to meiotic nondisjunction of chromosome 21 during ovum formation.

Mental retardation
Epicanthic folds
Flat facial profile
Cardiac malformation

46
Q

Down syndrome increased risk of Leukima by ______ times.

A

10-20 times

47
Q

What are cytogenetic disorders involving sex disorders?

A

Klinefelters syndrome = male hypoganthism when there are at least 2 X chromosomes and one or more Y chromosomes *Phenotypically patients are males.

Turner syndrome: partial or complete absence of one of the X chromosomes.

48
Q

What are the manifestations of klinefelters syndrome?

A
  • increased length of lower limbs; reduced body hair; gynecomastia; hypogonadism- most common cause of male sterility.
    Dentally = increased frequency of taurodontism.
49
Q

What are manifestations of turners syndrome?

A
  • short stature
  • webbing of neck
  • “shield like” chest
  • high arched palate
  • failure to develop secondary sex characteristics (primary amenorrhea)
50
Q

What are indications for genetic analysis?

A

Prenatal:
Mothers age >34yrs
Parent is carrier of a chromosomal translocation or x-linked disorder.
History of previous child with chromosomal abnormality

Postnatal:

  • Multiple congenital anomalies
  • unexplained mental retardation or developmental delay
  • suspected aneuploidy (downs)
  • infertility
  • Multiple spontaneous abortions.