Genetics Foundations, Chromosomes, Chromosomal Abnormalities, Imprinting (Lectures 11,12,21) Flashcards
law of independent assortment
any two genes will be inherited as independent units
the exception is linked genes
pleiotropy
a single mutation affects different organ systems
incomplete penetrance
the possibility that an individual can carry a particular genotype, but never show symptoms of the disease
nucleosome
- composed of 8 histone proteins
- structure around which DNA is wrapped to be condensed into chromatin
- the tighter a segment of DNA is wrapped around a nucleosome, the more difficult it transcriptional machinery to reach
- ie, a building block of a chromosome
law of segregation
allele pairs separate during gamete formation
linked genes
if 2 genes are very close together on the chromosome, they can be inherited together, and can only be separated by recombination events that occur during meiosis
the probability of recombination btw two loci is directly proportional to the physical distance that separates them on the chromosome (the closer they are, the less likely they will be separated)
heterochromatin
tightly wound DNA, genes are not actively transcribed
euchromatin
loosely wound DNA, genes are actively transcribed
incomplete dominance
each genotype has a different phenotype
sporadic mutation
individuals expose themselves to an environmental factor that phenotypically mimics, or phenocopies, a condition present in a family
karyotype
-Chromosomes stained with Giemsa stain in metaphase
-Dark bands are gene poor, have heterochromatin (also AT rich regions)
Light bands have euchromatin
When to karyotype / profile chromosomes
- Problems in early growth and development
- Stillbirth and neonatal death
- Infertility
- Family history
- Neoplasia
- Pregnancy for mother of advanced maternal age
Tissue source: blood, cheek swab, amniocentesis
aneuploidy
- abnormal number of chromosomes (ie, like 45, 47)
- differs by a fraction of the genome, not by multiples of the genome
Mitotic (post-zygotic) nondisjunction
establishes an abnormal line of cells within an otherwise normal individual
non-invasive pre-natal screening
meiotic nondisjunction
- a single chromosome is mis-segregated in the gamete
- occurs in oocytes more often than spermatocytes
Turner syndrome
only viable monosomy (X)
diagnosis at birth or puberty
webbed neck, short stature, lymph edema in hands and feet
infertility, amenhorrea, normal intelligence
klinefelter syndrome
- trisomy XXY
- long limbs
- hypogonadism (small genitalia)
- gynecomastia
- infertility (no germ cells)
- behavioral, IQ difficulties
balanced rearrangements
genomic content is shuffled such that everything remaining is the same copy number (of genes)
examples include: inversions, translocations: Robertsonian + reciprocal
unbalanced rearrangements
net loss/gain of genomic content
examples include: translocations, duplications, deletions
inversions
-occur when a chromosome experiences one or two double-stranded breaks, and the liberated fragment is re-inserted into the chromosome in the opposite orientation
two main types:
-paracentric: not involving the centromere
- pericentric: involving the centromere
- breakpoints in the chromosome can disrupt the a gene’s function
reciprocal translocation
- when two or more chromosomes has dsDNA breaks and the material is exchanged before the breaks are repaired
- DNA relocates to a new chromosome with no net gain or loss of material
- A notable translocation is between chromosomes 9 and 22, which harbor a novel fusion protein resulting from joining of two genes at the break point (bcr-abl fusion protein results in increased and mislocalized tyrosine kinase activity, resulting in the development of chronic myelogenous leukemia, CML).
spectral karyotyping (SKY)
- individual probe sets labeled in 24 different colors for each unique chromosome
- makes it easy to determine origin of “extra” DNA
- Easier to characterize translocations
Cri-du-Chat syndrome
- terminal deletion of chromosome 5 (5p15)
- Loss of this chromosome segment causes patients to cry with a characteristic cat-like sound and develop intellectual disability, microcephaly, epicanthal folds, low set ears, and heart defects
chromosomal microarray (CMA)
- fetal DNA is analyzed to determine if loci are over- or -under represented in the sample
- high resolution method of counting copies of genomic loci
- More effective at detecting small-scale chromosomal changes that can be missed by traditional karyotype analysis
- Can’t detect balanced rearrangements because it is not able to provide spatial info about chromosome arrangement
Edwards syndrome
trisomy 18
Patau syndrome
trisomy 13
