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Chapters 5 & 11 Genetics

front 1

Most accessible cells that are capable of proliferation in culture?

back 1

White Blood Cells (T lymphocytes)

front 2

Short term & long-term cultures are taken from samples of skin biopsy -->

back 2

cultures from cells produce fibroblasts, which can be used for biochemical, molecular studies, chromosome and genome analysis

front 3

WBCs can also be transformed in culture to form -->

back 3

Lymphoblastoid cell lines (HeLa cell is an immortal cell line. Oldest and most commonly used. Line derived from cervical cancer cells)

front 4

Fetal cells are derived from

back 4

amniotic fluid

front 5

Contributions HeLa Cells have made to science include (5):

back 5

1. Polio vaccine

2. Improved cell culture practices

3. Chromosome counting

4. Genome mapping

5. Human Papilloma Virus (HPV) vaccines

front 6

What does 46, XX, del(5)(q13) mean?

back 6

Female with terminal deletion of one chromosome 5 distal to band 5q13

front 7

What does 46, X, r(X) mean?

back 7

Female with ring X chromosome

front 8

What does 46, XX, t(2;8)(q22;p21) mean?

back 8

Female with balanced translocation between chromosomes 2 and 8, with breaks in bands 2q22 and 8p21

front 9

What does 47, XX, +21 mean?

back 9

Female with trisomy 21

front 10

What does 45, XY, -22 mean?

back 10

Male with monosomy 22

front 11

Dividing cells are arrested in .... by ......

back 11

Metaphase, destroying spindle fibers and shortening chromosomes

front 12

Clinical indications for chromosome and genome analysis (6):

back 12

  1. Problems of early growth & development
  2. Stillbirth & neonatal death
  3. Fertility problems
  4. Family History (abnormalities among relatives)
  5. Neoplasia (chromosome & genome evaluation in tumor or bone marrow)
  6. Pregnancy (women older than 35)

front 13

Base Substitution

back 13

mutation involving a base changing to a different base

front 14

Inversion

back 14

a stretch of DNA breaks off and reattaches in the opposite orientation

front 15

Insertion & Deletion

back 15

One/several bp added & deleted

front 16

Translocation

back 16

a stretch of DNA breaks off then reattaches somewhere else

front 17

Mispairing

back 17

A not pairing with T OR G not pairing with C

front 18

Aneuploidy

back 18

X & Y chromosomes

Autosomes

front 19

Structural abnormalities

back 19

Balanced & Unbalanced

front 20

Ring Chromosomes occur

back 20

in a mosaic state. 1 in 2500.

front 21

Molecular disorders: primary disease-causing even is an alternation either inherited or acquired -->

back 21

affecting a gene(s), its structure, and its expression

front 22

DNA sequencing alternations --> (2)

back 22

  1. amount or function of mRNA or protein --> diseases
  2. amount or function of noncoding RNAs (ncRNAs), including miRNA --> diseases

front 23

Mutations involving protein-coding genes -->

back 23

cause disease through one of four different effects on protein function

front 24

Four different effects are:

back 24

  1. Loss of Function (MOST COMMON)
  2. Gain of Function
  3. Novel Prperty Mutations
  4. Mutations associated with heterochronic or ectopic gene expression

front 25

Mutations involved in gene regulation are likely located in

back 25

Conserved or functional important

front 26

Mutations involved in RNA stability are likely located

back 26

at 5' or 3' UTRs

front 27

Other mutations include: (3)

back 27

  1. Silent: AA doesn't change
  2. Nonsense: AA changes to STOP
  3. Missense: conservative (AA has same property) & non-conservative (AA does not have same property)

front 28

Four mutations cause loss of function to the protein: (4)

back 28

  1. Missense
  2. Nonsense
  3. Frameshift
  4. Splice Site

front 29

Loss of Function Mutations: Deletion -->

back 29

Reduction in gene dosage

front 30

Gain of Function Mutations: Increase of one or more of protein functions -->

back 30

Increases gene dosage (gene duplication in amyloid precursor protein gene in AD)

front 31

Novel Property Mutations: Infrequent, amino acid sequence --> novel property on protein (sickle cell) -->

back 31

no effect on ability of sickle hemoglobin to transport oxygen

front 32

Mutations associated with Heterochronic or Ectopic Gene Expression: mutations --> inappropriate expression, regulatory regions -->

back 32

cell proliferation (oncogene) ex. cancer is due to abnormal expression

front 33

Any one of these 8 stages will disrupt normal productions of a protein

back 33

  1. Transcription
  2. Translation
  3. Polypeptide Folding
  4. Post-translational modification
  5. Assembly of monomers into a holomeric protein
  6. idk
  7. Cofactor or prosthetic group binding to the polypeptide
  8. Function of a correctly folded, assembled, and localized protein produced in normal amounts

front 34

Allelic Heterogeneity

back 34

multiple alleles at a single locus, ex CFTR

front 35

Locus Heterogeneity

back 35

mutations in more than two genes --> special clinical condition like thalassemia from either beta or alpha globin chain

front 36

Six types of human hemoglobin

back 36

  1. Hb Grower 1
  2. Hb Grower 2
  3. HB Portland
  4. Hb F (alpha2gamma2)
  5. HbA2 (aplha2delta2)
  6. HbA (alpha2beta2)

front 37

LCR

back 37

Locus Control Region

front 38

Expression of beta globin gene is only partly controlled by

back 38

the promoter and two enhancers

front 39

20 kb deletion upstream of LCR of beta goblin complex -->

back 39

disease since LCR is required for gene expression

front 40

Hemoglobin disorders: First Group

Structural Variants

back 40

ex. Sickle cells due to mutation --> deoxygenated beta goblin relatively insoluble --> changing shape of red cell

front 41

Hemoglobin disorders: Second Group

Thalassemias

back 41

structural variant --> destabilizes the chain --> decreases production of a globin chain --> decreases abundance of chains --> ratio of alpha to beta chains imbalance due to promoter mutations

front 42

Hemoglobin disorders: Third Group Hereditary persistence of fetal hemoglobin

back 42

benign conditions. impair perinatal switch from gamma globin to beta globin synthesis.

ex, deletion removes both delta and beta globin genes but leads to continued postnatal expression of the gamma globin genes to produce Hb F, an effective oxygen transporter

front 43

What kind of mutation causes sickle cell?

back 43

Base substitution mutation. GAG to GTG. Glutamate to Valine. Reduced oxygen carrying efficiency

front 44

Hemoglobin Structural Variants

400 abnormal hemoglobins, 50% are clinically significant.

Variants --> hemolytic anemia --> tetramer unstable

Variants with altered oxygen transport are due to ......

back 44

increased or decreased oxygen affinity or to formation of methemoglobin --> form of globin incapable of reversible oxygenation

front 45

Hb Kempsey

  1. Amino Acid substitution?
  2. Pathophysiological Effect?
  3. Inheritance?

back 45

1. Beta chain. Asp99Asn

2. Substitution keeps Hb in its high oxygen affinity structure --> less oxygen to tissues --> polycythemia

3. AD