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One Carbon Metabolism and Epigenetic in fetal plasticity.

Research estrogen assays.

The following are indicative of positive selection for a particular trait:

• Low Macrosatellite Variability
• High Linkage Disequilibrium

The Hardy-Weinberg Equilibrium states that the allelic as well as genotype frequencies and distribution in the offspring population would be similar (or in equilibrium) to the ones in the parent population just by chance unless specific disturbances are introduced.

Deviations from HWE are caused by some demographic scenarios such as:

• Natural Selection
• Population Bottlenecks
• Reduction of population sizes
• Founder Effect
• Non-random mating
• Mutations
• Genetic Drift
• Gene Flow

These demographic scenarios can be identified by:

• Simulating expected pattern of variation under different scenarios (Computer Modelling)
• The Outlier approach

Outliers show an unusual pattern of variation or population differentiation compared with empirical data collected from other loci across the genome.

Two deadly abilities.

• Are macro-evolutionary principles applicable to cancer cells?

• Metastatic dissemination occurs continually throughout the course of primary tumour development, yielding a diverse spectrum of disseminated cells, including ones that are at the moment of dissemination almost indistinguishable from normal cells. <-- Do these exhibit any characteristics of cell stress? Can these targeted by the T-cells.

Phenomenon where the allelic distribution in the offspring population differs significantly from the allelic distribution in the parent population because of a purely random selection of allelic variants at the parent population level. This selection of which individuals (and thus which allelic variant) from the parent population go on to reproduce could also be chosen through selection pressures. When the offspring population is different in its allelic distribution due to chance alone, its called genetic drift. In a small population, genetic drifts (due to random fertile individual selection) are much more likely to happen as compared to large populations. Genetic drift often introduces more allelic homogeneity among the offspring generation population (eg. Non-African Populations).

Thus, reasons for offspring allelic frequencies being different from parent gene pool allelic distributions:

• Founder effect
• Genetic Drift
• Selective pressure (due to climate, diet, infections etc.)

Related Terms:

• Hardy-Weinberg Equilibrium: The principle that parent and offspring allelic distribution will remain fairly similar from generation to generation.

Exceptions to the Hardy-Weinberg Equilibrium happen due to selective evolution, founder effect or genetic drift.

• Markov Property: The predicted distribution of alleles in the offspring population is not dependent on any grand-parent allelic distributions. They are thus memory-less and only dependent on parent allelic distributions.

In small populations: (Non-Africa)

• Genetic Drifts play a larger role in determining final offspring population allelic frequencies

In large populations: (Africa)

• Even weak selection forces are predicted to influence final offspring population allelic frequencies because random chance always predicts more uniformity among parent and offspring allelic distributions.

Population Bottleneck: A catastrophic event that reduces the size of a population thus exposing this resulting smaller population to all the effect of a genetic drift in the future. This might lead to a founder event.

Coalescent Theory: Tracing back ancestors to see when two distinct populations with different allelic distributions shared a common coalescent parent. The probability that two lineages coalesce in the immediately preceding generation is the probability that they share a parent.

• Rapidly expanding populations: Rare polymorphisms also expand.
• Population Bottleneck: Loss of low-frequency rare variants.

During founding events, the particular pattern of pairwise allelic association might have differed from the parental African population, depending on the genetic constitution of the founders relative to that of the parental gene pool. Only a few individuals from the parent gene pool that are responsible for establishing a wholly different population group. This population group has far less diversity as compared to the parent gene pool simply because it started out with a fewer number of individuals. Thus:

• LD blocks are longer
• More linkage disequilibrium
• Less markers needed
• Start association studies with these populations
• Use preliminary results to then study the effects of finer diversity in African Populations.

There are three types of Evolution

• Selective Evolution

Elimination of diversity and retention of just the phenotypes (and genotypes) that can withstand the evolutionary pressure.

• Adaptive Evolution

Introduction of diversity as a means to combat evolutionary pressures. Important for how environment shapes our genomes.

• Stochastic Evolution

Allelic selection by chance alone eg. genetic drift. (Not strictly evolution).

The Code to the Book of Life

• Locus -> Position of any of the following elements in the book, specified by a number-alphabet sequence.
• Locus Example -> (Chromosome, Arm, Region, Band, Sub-band) -> (Chapter, Section, Page, Paragraph, Line)
• Bases -> Alphabets
• Genes -> Sentences that add to the story.
• Sections of DNA -> Paragraphs
• Chromosomes -> Chapters
• Arms of the Chromosomes -> Sections within the Chapters. p (short arm); q (long arm)
• Centromere -> Planned Break in the Chapter between Sections
• Region of the Chromosome -> Specified range of pages within sections of a chapter
• Band of the Chromosome -> Paragraph/s of interest within a given region
• Sub-band of the Chromosome -> Lines of interest in a given region
• Tangible structures made of proteins -> Story
• Complete human body -> Novel
• Population -> Library

Variations

• Structural Variants -> Differences of a group of words collectively made up of larger than a thousand (1kb) alphabets or bases.

• Copy Number Variation -> Group of words (made up of larger than a 1000 alphabets - 1kb) that repeat a varied number of times in different books. These may include insertions, deletions and duplications. Large Scale CNVs are more than 50,000 alphabets long. They can be detected by clone-based array comparative genome hybridization (array-CGH)

• Copy Number Polymorphism -> A CNV (an allele with a specific number of > 1kb repeats) that occurs in more than 1% of the population.

• Microsatellite: Two, Three or Four Alphabet Repeat. In a polymorphism, these di/tri/tetra alphabets are repeated a varied number of times at the same locus. Alleles are the loci with different numbers of repeats. Microsatellites with few variant alleles come from populations with a low frequency of mutation whereas alleles with many variant microsatellites come from populations with a high frequency of mutations. Individuals that are most closely related will have the most similar alleles at each, of the many examined, loci. Thus, similarity of fingerprints will provide the necessary information.

• Single nucleotide polymorphism -> Single Alphabet Typo

In some individuals, whole paragraphs of the text were duplicated, whereas in others, large passages were missing, or even printed backwards. These major revisions turned up in all kinds of people, including many who seemed healthy and normal. Suddenly, it seemed possible that there was actually no standard version of the Book of Life, and researchers wondered whether we are all much more different from each other than they had thought. In the Book of Life analogy, polymorphisms in copy number variations are sections of text where certain paragraphs are repeated different numbers of times in different individuals. The single nucleotide polymorphisms or SNPs are merely the single-letter ‘typos’ in the Book of Life.

Practically, some of the genes, if duplicated, can have beneficial or deleterious effects on a person's susceptibility to a diseases and prognosis of the disease. Extra copies of CCL3L1, helps protect people against HIV. Extra copies of CCL3L1 delay the progression of HIV positivity to AIDS.

Structural Variation would be important in the context of polygenic and complex diseases - when just one gene or one SNP does not explain variations in disease distributions. If a huge chunk of DNA varies among populations, explaining polygenic influences on a disease would be more plausible.

Gene-Environment interactions may also be explained better with the structural variation model. If regions of structural variation in human beings are still evolving - then these might be the locations that are gradually targeted for selection among people who are suited to a post-paleolithic environment and people who aren't. Thus should we be looking at structural variations that have been selected already instead of SNPs? Should we be looking at the paragraph scale of evolution and not at an alphabet or sentence scale - when we look at evolutionary natural selections? Structural Variation might well be responsible for our divergence from the apes in the evolutionary tree.

Where to look for these trouble-causing CNVs, and indels.

• Segmental Duplications - 5% of the genome. A segment of DNA greater than a 1000 bases (alphabets) in size that occurs in two or more copies per haploid genome. Each copy shares a greater than 90% sequence identity with each other (is more than 90% similar).

• Regions of inversions (which in turn occur in regions of segmental duplications: Reversed in orientation with respect to the rest of the chromosome - A palindrome? Pericentric involves the centromere. Paracentric don't.

Copy number variation is the number of duplications, insertions and deletions of the same segment of the DNA in different individuals. Thus a "control" group that is normal may not necessarily be "normal" or even comparable to the cases who have the CNVs. If the same copy numbers variation occur in more than one individual, at the same location, they are "polymorphisms" - particular spots that regularly differ between individuals. More than one person has an alternative copy number variant of that particular stretch of DNA.

However, the range of what is normal might be quite wide when it comes to structural variation. Normal people might have a wide variety of structural variation.

Immune cells activated against estrogen receptors?