Genetics In Biological Processes Flashcards
Genetics of biological processes can be divided into 3 main categories:
- Developmental genetics (including genetics of sex)
- Oncogenetics
- Immunogenetics
Developmental Genetics:
What us a Totipotent cell?
Totipotent cell (e.g. fertilized egg): can become any cell and construct a viable organism
Developmental Genetics:
What us a Pluripotent cell?
Pluripotent cell (e.g. inner cell mass, epiblast): can become almost any cell type
Developmental Genetics:
What us a Multipotent cell?
Multipotent cell (embryonic endo / meso / ectoderm): can become some cell type (from germ layers)
The use of stem cells (cultured pluripotent cells) can be applied to:
− Drug development and toxicity test
− Experiments to study development and gene control
− Tissue / cell therapy (e.g. nerve cells, heart cells, pancreatic -cells)
What are *iPS (induced Pluripotent Stem) Cells?
iPS (induced Pluripotent Stem) Cells: production of pluripotent stem cells from a donor which is undergo
cell programming for stem cell therapy (e.g. nerve cells, heart cells, pancreatic -cells)
Stem Cell Fate:
What are the intrinsic factors the Lineage is influenced by?
− Asymmetric division
− Uneven distribution of receptors, transcription factors
Stem Cell Fate:
What are the extrinsic factors the Positional identity is influenced by?
− Morphogens
− Cell-cell interactions
− Cell-matrix interactions
What is a Morphogen?
Morphogen: soluble signaling molecule with concentration gradient in eggs or developing embryos.
Act differently on the same target cell type, depending on their location.
What are examples for morphogens?
- Activin (TGFbeta)
- Sonic Hedgehog
- Retinoic Acid
Sex Determination Genes:
SRY - Is it anti-Testis or anti-Ovary?
SRY - Anti-Ovary gene.
aka Sex-determining Region of the Y chromosome
Sex Determination Genes:
RSPO1 - Is it anti-Testis or anti-Ovary?
RSPO1 - anti-Testis
R-spondin1, on chromosome 1
Sex Determination Genes:
WNT4 - Is it anti-Testis or anti-Ovary?
WNT4 - anti-Testis
Sex Determination Genes:
SOX9 - Is it anti-Testis or anti-Ovary?
SOX9 - anti-Ovary
found on chromosome 17
Sex Determination Genes:
Beta-catenin - Is it anti-Testis or anti-Ovary?
Beta-catenin - anti-Testis
Sex Determination Genes:
FOXL2 - Is it anti-Testis or anti-Ovary?
FOXL2 - anti-Testis
Sex Determination Genes:
DAX1 - Is it anti-Testis or anti-Ovary?
DAX1 - anti-Testis
Sex Determination Genes:
CBX2 - Is it anti-Testis or anti-Ovary?
CBX2 - anti-Ovary
Sex Determination Genes:
MAP3K4 - Is it anti-Testis or anti-Ovary?
MAP3K4 - anti-Ovary
Abnormalities of Sexual Development:
abnormal crossing-over during male gametogenesis (meiosis I) results in either 2 possibilities - what are those?
Abnormal crossing-over during male gametogenesis (meiosis I) results in:
- 46 chromosomes XX Male (SRY transfer to X)
- 46 chromosomes XY Female (SRY loss in Y)
Abnormalities of Sexual Development:
What is the Androgen Insensitivity syndrome?
Androgen Insensitivity syndrome: Testosterone receptor mutation, XR.
Female features in XY genotype causes Infertility
Abnormalities of Sexual Development:
What is the Kallmann syndrome?
Kallmann syndrome: Mutations in KAL1 gene, Chromosome X (PAR1). Cell adhesion protein deficit, lack of migration leading to loss of smell sense with NO GHRH - failure in gonadal differentiation.
Abnormalities of Sexual Development:
What are PAR1 and PAR2?
PAR1 and PAR2
Pseudoautosomal Region of X chromosome. short regions of homology between the mammalian X and Y chromosomes. (Recombine like autosomal).
Oncogenetics:
What percentage of Tumors arise in a pattern of Mendelian inheritance? (rest being complex trait)
Tumors with Mendelian inheritance - Less than 10%
Oncogenetics:
Majority of cancers are caused by mutations in SOMATIC/GAMETES cells?
Somatic cells
Oncogenetics:
What are Driver mutations?
Driver mutation: confers a selective growth advantage.
Responsible for growth of tumor and influence survivability of the tumor.
Oncogenetics:
What are Passenger mutations?
Passenger mutation: has no effect on the fitness (i.e. survivability) of a clone.
What are the 3 most commonly mutating driver genes of tumors?
Driver genes of tumors:
- Oncogenes
- Tumor Suppressor Genes
- Mutator Genes
The 2 most common mutations in tumors affect: (they occur in > 60% of all cancers)
most common mutations in tumors:
− The RAS oncogene
− The P53 tumor suppressor gene
Gain-of-function mutation of a _____________ , which leads to an oncogene.
Gain-of-function mutation of a PROTO-ONCOGENE, which leads to an oncogene.
Loss-of-function mutation of a ___ ________ gene.
Loss-of-function mutation of a TUMOR SUPPRESSOR gene.
What is Loss of Imprinting (LOI)?
Loss of Imprinting (LOI): a case of genome hypomethylation, by which a gene is “reactivated”.
Loss of the original pattern of imprint, causes abnormal imprinting.
What is Loss of Heterozygosity (LOH)?
Loss of Heterozygosity (LOH):
The loss of one allele of a genetic locus can have multiple possible functional effects including
haploinsufficiency, loss of gene expression and being the second ‘hit’ that unmasks (Only) a recessive tumor
suppressor gene.
Immunogenetics:
the heavy chain variable region has three domains - what are those?
V (variable), D (diversity) and J (joining)
Immunogenetics:
the light chain variable region has 2 domains - what are those?
V (variable), and J (joining)
Somatic Gene Rearrangement (or Somatic Recombination): When does this happens?
active only during the T-and B-cell
maturation
Somatic Gene Rearrangement (or Somatic Recombination):
What are the enzymes responsible for DNA splicing? What is the result?
RAG1/2 enzymes give a “mix” of different V-D-J.
Somatic Gene Rearrangement (or Somatic Recombination):
What is the result of mRNA splicing?
Further rearrangements of V-D-J and switch from the membrane-bound IgM C domain to the soluble IgM C domain.
Somatic Gene Rearrangement (or Somatic Recombination):
What is the function of Tdt?
TdT (terminal deoxynucleotidyl transferase):
Recombination can be shifted (frame shift) a few
bases in 5’ to 3’ direction.
Somatic Hypermutation:
What is it part of?
Affinity Maturation
Somatic Hypermutation: What is it triggered by?
Activation induced cytidine deaminase (AID), which deaminates cytosine to uracil. This base mismatch, which not repaired by any mechanisms, can result in a number of different mutations.
Somatic Hypermutation: Immunoglobulin Class Switching - How is it achieved?
DNA splicing (Third time in B cell maturation process)
Immunogenetics - Role of Epigenetics:
Histone modifications and Subsequent chromatin remodeling create a so-called ___________ _____, thus the Ig or TCR regions become accessible by RAG recombinases.
Immunogenetics - Role of Epigenetics:
Histone modifications and Subsequent chromatin remodeling create a so-called RECOMBINATION CENTER, thus the Ig or TCR regions become accessible by RAG recombinases.
Where frequency of Nondisjunction higher: Spermatogenesis/Oogenesis
Oogenesis
Where frequency of Replication errors higher: Spermatogenesis/Oogenesis
Spermatogenesis
Where frequency of Crossing over higher: Spermatogenesis/Oogenesis
Oogenesis
