Chromosome & Gametes Flashcards
(21 cards)
What are the fundamental principles of evolution?
Reproduction: the ability to reproduce to pass on genes on to the next generation.
Variation: the replicating system must undergo changes. Each new generation either reproduces or dies out.
What are the requirements for asexual reproduction.
it must be able to:
o Replicate
o separate its 2 copies @ mitosis
o maintain itself between generations
What is an allele?
one version of a particular gene
- Each parent passes on one allele (i.e. one version of a particular gene) to each offspring
- Abnormalities in alleles can be passed on or can be compensated for depending on what you inherit from each parent
- Consanguineous relationships lose the ability to filter out common mutations
- If alleles are heterozygous the phenotype of the trait can dominant or recessive.
Gene transcription and translation
- Promotor and coding sequence transcribed into a gene product
- Introns are removed from exon by splicing
- mRNA exported out of nucleus
- Translated into proteins in ribosomes i.e. complexes of tRNA and proteins
- Proteins then folded into unique 3D structure that determines function
• How can the same gene be tissue specific?
By having alternative promoters
- CYP19A1 codes for aromatase (aromatase is an enzyme that catalyses androgens oestrogen)
- Aromatases can be found in – breast, ovary, placenta, adipose tissue and brain tissue
- CYP19A1 uses different promoters in breast, ovary and brain
- Exons 2-10 is a coding region which codes for the aromatase protein
- Production of aromatase is controlled by a common splice site found upstream of the coding region
- On this splice site, you can attach different exon 1’s (which are not coded), which have special regulatory regions containing promoters, and these promoters will then drive the transcription of the remainder of the gene to make your enzyme.
- In ovary, it has promoter 2 (PII), this promoter in exon 1 is attached to the splice site and this promoter will respond to different hormones (FSH, insulin) that will drive exons 2-10 to make aromatase.
- In breast, it is promoter 1.4, that responds to different growth factors and substances, which switches on aromatase in the breast to make oestrogen
In woman who are post-menopausal (no ovarian function, not producing oestrogen from ovaries), you often get oestrogen-dependent breast cancer
o Due to abnormal activation of various promoters in the breast = breast tissue produces oestrogen = breast cancer
o In breast, androgens are accessed from the functional adrenals
How can one gene give rise to several products?
alternative splicing of exons
products are known as Isoforms.
eg. 3 alternatively spliced variants of human FSHR found in testicular tissue – possible association with spermatogenic defects
although the overall gene when investigating infertility may appear normal, its functionality may be compromised through alternative splicing
How can the protein be modified once made?
o Post-translational modification e.g. phosphorylation (makes protein active)
o Glycosylation i.e. adding on carbohydrates to protein, making protein more stable and soluble. This is how FSH and LH are modified in the endoplasmic reticulum.
o Often hormones secreted as “pro-hormones” and must be enzymatically processed to form the active hormone (e.g. pre-proGnRH, insulin)
What are Somatic Cells?
diploid cells that replicate by simple cell division (mitosis)
o give identical progeny + usually have limited number of divisions
o e.g. hepatocytes, pancreas, skin cells
What are the advantages of sexual reproduction?
o Prevents the accumulation of genetic mutations
o Increase in genetic diversity
o Maintenance occurs because of the advantage of genetic variability
o Variation in off-spring → Better able to evolve and adapt to changing environment
What is the origin of X and Y chromosome?
differentiated from a pair of identical chromosomes (autosomes)
ancestral mammal developed a variation which made it male…. gradually this chromosome became the Y and the other the X
with evolution, genes advantageous to either sex became focussed on X or Y.
What are gametes?
- haploid cell specialized for sexual fusion
- contain 23 chromosomes in total
- Unlike other cell gametes, these cells divide by going through cycles of diploidy and haploidy
What is the origin of gametes
- Gametes originate from germ line cells: primordial germ cells that migrate into the gonad and then differentiate to either male or female gametes
- The process producing oocytes – oogenesis (incorporated as part of folliculogenesis)
- The process producing sperm - spermatogenesis
- Undergo cycles of mitosis to increase numbers
- Then undergo meiosis
- Then combine at fertilisation
Explain Mitosis
- Interphase:
• Uncondensed chromatin DNA duplicated to the sister chromatids
• The centrioles are also duplicated: 2 centrioles
• As centrioles duplicate, they form a spindle made up of microtubules.
• This then enters mitosis, where the DNA wraps around histones and become condensed, leaving a condensed duplicated chromosome held by a centromere - Prophase:
• Chromosomes condense – they wrap around histones forming a compact structure and they start to move to align themselves
• The nuclear envelope breaks down and outside the nucleus in the cytoplasm, the two centrioles will migrate to opposite poles of the cell to initiate formation of mitotic spindles (made from microtubules) - Metaphase:
• Chromosomes (consisting of two chromatids) line up at the equatorial plane of the cell – and the crucial part is how they align themselves as this is different in mitosis from meiosis
• In mitosis: they line up one after the other
• E.g. chromosome 1 from mum, chromosome 1 from dad, chromosome 2 from mum etc…
• There will be 23 pairs of chromosomes (46) aligned in the center - Anaphase:
• Microtubules attach to kinetochores (proteins in the centromere which allow attachment) and shorten so the sister chromatids are pulled apart from the centromere migrate to opposite ends - Telophase:
• nuclear membrane forms, so you have two new nuclei – each with two complete sets of chromosomes - Cytokinesis
• divides the cell cytoplasm into two daughter cells – exact copy of the mother cell
What is the difference between Mitosis and Meiosis?
o Mitosis: cell divides to produce 2 new ‘daughter’ cells that are identical to the original and diploid
Involves one cell division. Produces two diploid cells. Occurs in somatic cells. Results in growth and repair. No exchange of genetic material. Daughter cells are genetically similar.
o Meiosis: similar to mitosis but more complex → results in production of ‘daughter’ cells that are non-identical and haploid
Involves two cell divisions.
Produced up to four haploids cells.
Occurs only in ovaries and testes during the formation of gametes (egg and sperm)
Results in gamete production
Parts of chromosome are exchanged during crossing over
Daughter cells are genetically dissimilar
How is meiosis advantageous?
o random distribution of male and female homologous chromosomes
o chromosomal crossing over occurs
How is genetic variability achieved?
Independent Assortment
• homologous pairs of chromosomes line up at the equator (midpoint) of the spindle during metaphase I.
• However, the orientation of the members of the pair is random with respect to which member is closer to which pole.
Crossing Over (Recombination) • Corresponding pieces of chromatids of maternal and paternal homologues (non-sister chromatids) are exchanged during synapsis when the homologues are aligned side by side. • Each of the affected chromatids has a mixture of maternal and paternal genetic information
Do Sex chromosomes cross over?
• Sex chromosomes align but crossing over does not usually occur in X and Y chromosomes apart from at the pseudoautsomal regions (PAR)
• Why?
o They are hemizygous to each other & so recombination proved harmful
o PAR allows the X & Y chromosomes to pair and properly segregate during meiosis in males
• X-inactivation occurs in which one of the copies of the X-chromosome is silenced to prevent females from having twice as many gene products as males.
o Choice of which is inactivated is random in placental mammals like humans.
What is an aneuploidy?
- A gain or loss of chromosomes from the normal 46 is called aneuploidy, affecting normal development and functioning.
- Since each chromosome contains hundreds of genes, the addition or loss of a single chromosome disrupts the existing equilibrium of the cell leading to profound phenotypes.
o Majority occur from an error in maternal meiosis I because human oocytes are arrested in prophase I for decades
Majority are lethal
o E.g. trisomies (47 chromosomes) account for 35% of spontaneous abortions/miscarriages
• Most common aneuploidies in humans are trisomies (0.3% of live births).
• Viable ones are:
o Trisomy 21 (aka Down’s syndrome, 1:750 births)
o Trisomy 18 (Edwards syndrome)
o Trisomy 13 (Patau syndrome)
Define non-disjunction
failure of homologous chromosome to separate during MI or sister chromatids to separate during MII, resulting in extra or missing chromosomes
Examples of sex chromosome aneuploidy
more viable, usually random event (not inherited):
o Turner syndrome (45, X monosomy) caused by complete or partial absence of 2nd sex chromosome (occurrence 1:2000 female births) → phenotype=short stature, primary amenorrhea (classic Turners)
o Klinefelter syndrome (47,XXY trisomy) caused by presence of two X and one Y chromosome (occurrence 1:500 male births) → variable phenotype= taller than average, small testes producing reduced testosterone, infertility
What are the mechanisms which contributes to the maternal age effect on the risk of trisomy?
- Recombination failure
- Premature homologue separation
- Premature sister chromatid separation due to loss of cohesion between sister centromeres
