Human Genetics
Mariam55Multifactorial Developmental Traits
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Cells express phenotypes
inherited traits, acquired traits, illnesses
X-linked Duchenne muscular dystrophy has cellular phenotype before whole-body symptoms appear– lack of dystrophin protein causes muscle cells to collapse when contracting.
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Tissue Types
differentiated cells
290 types of somatic cells
sperm or egg cells
stem cells
divide to differentiated cells
replicate through self-renewal
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Generalized Animal Cell
number and type of organelles differ based on cell type/function
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Specialized cells: secretion of milk
secretion of milk is a phenotype of mammary gland lactating cells
requires organelles important in secretion
RER
Golgi
vesicular transport
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Deficiencies of organelles cause disease
lysosomal storage disease: Tay-Sachs
cells rely on number of lysosomes
essential for normal brain function
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Inefficiencies of organelles cause disease
mitochondrial myopathies
inefficient cellular respiration leads to ROS
ROS destroys enzymes, DNA
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Deficiencies of cell-to-cell communication
plasma membrane surface molecules
signal transduction
receptors detect signals from outside the cell and transmit them inward
small molecules, antigens, electrical impulses, mechanic changes, thermal changes, etc.
cellular adhesion
molecules help cells attach to other cells
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epidermolysis bullosa is a defect in skin attachment
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Normal cell division and death
growth, development, repair, healing
balance of mitosis/cytokinesis and apoptosis
precise, genetically programmed sequence of events
required for shaping limbs
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The cell cycle is controlled molecularly
molecular checkpoints in cell cycle
internal and external factors affect mitotic clock
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Mitosis regulated by hormones, growth factors
hormones are produced by glands
transported in bloodstream to body
binds specific receptor
growth factors are produced by cells
act locally, near site of production
binds receptor type
e.g., Epidermal Growth Factor (EGF) released by damaged cell, stimulates cell division in skin beneath scab
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Linear chromosomes protected by telomeres
hundreds to thousands of 6-base repeats
50-200 bases lost after each cell division
after 50 divisions, shortened telomeres signal cell to stop dividing:
most cells go through apoptosis
some cells produce telomerase to correct ends, avoid apoptosis
sperm, eggs, bone marrow, and cancer cells
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Stem cells are immortal
divides by mitosis
stem cell
progenitor cell
does not renew
differentiates
active telomerase
maintains chromosome ends
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Pathways to Cell Specialization
totipotent
can give rise to every cell type
pluripotent
fewer possible fates
multipotent
few developmental choices
unipotent
one developmental choice
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Stem cells replace unhealthy cells
human stem donor cells
embryonic stem cells (pluripotent)
using the inner cell mass (ICM) of an embryo
differentiate into any cells of embryo (not trophoblast)
induced pluripotent stem (iPS) cells (multipotent)
reprogrammed somatic cells
differentiate into any of several cell types
adult stem cells (multi- or unipotent)
tissue-specific or somatic stem cells
differentiate into one or a few cell types
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Stem Cells in Health Care
to replace unhealthy cells
self-donor
matched donor
cardiomyocytes grown in a dish from iPS cells
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Human development is controlled
stages of mammalian development
zygote after fertilization
fusion of egg and sperm
cleavage
first divisions to multi-cell blastocyst
embryo for the first 8 weeks
embryonic plate develops from inner cell mass
fetus from the start of the ninth week until birth
growth and maturation
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Fertilization
formation of zygote
sperm are activated and drawn to the oocyte
sperm acrosomal enzymes aid sperm penetration
chemical and electrical changes in the oocyte surface block entry of more sperm
two genetic packages meet and merge
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Cleavage
formation of blastocyst
period of frequent mitotic divisions
solid ball of 16+ cells (morula)
hollowing of ball to blastocyst
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blastocyst is trophoblast (outer layer) + inner cell mass
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Imprinting errors cause disease
deletion of chromosome 15 imprinted region
Prader-Willi syndrome if deletion inherited from father (no active copy)
Angelman syndrome if deletion inherited from mother (no active copy)
Prader-Willi s. phenotype of obesity, NIDDM, excessive hunger, moodiness and conduct disorder
Angelman s. phenotype of failure to thrive, hyperactivity, muscle hypotonia, happy mood
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Importance of genomic imprinting
regulate abundance of key proteins in embryo
imprinted genes in clusters, controlled by imprinting centers
one gene in cluster could be essential
others imprinted in bystander effect
uniparental disomy
results in teratoma
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Changes in gene expression in development
over time, in different cell types
programmed differentiation of stem cells
cell, tissue, or organ/gland level
changes in sets of proteins available
everything in a cell is due to a gene product
inherited or acquired changes in gene expression: epigenetics
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