Good Genes Gone Bad EXAM 2

Neanderthal man and us

Sequencing of most of the Neanderthal genome and comparing that sequence to ours revealed that we are more closely related to this individual than we are to chimpanzees

Indeed, Neanderthals interbred with modern humans, which can be seen in our DNA

What can the information in the change of DNA from when Neanderthals interbred with modern humans offer us?

It is change in the DNA (in the form of "mutations") that generates variation, and this information can be used to track human migrations...

Studies on genes from different races have shown that there are no major discontinuities between the races, telling us that the race concept is not meaningful at the genetic level

What are the two approaches to trace the ancestry of human populations?

Lineage-based approach & Admixture testing approach

Lineage-based approach

- Uses markers on either the Y chromosomes (passed down from father to son) or on mitochondrial DNA (always maternally inherited)

- Genetic drift/subsampling of a population brings paternal/maternal mutation with them (always a subset of the entire range of mutations). Also called founder effect

- New mutations arise in the new "founder" population, creating a distinctive "marker" which differentiates this population from the previous. This mutation may even bee selected for if it gives some kind of benefit to the individual(s).

Admixture testing approach

- looks at many variants (SNPs) on all chromosomes and compares them with the variants present in different populations around the world (East Asian, European, Native American, etc.) to place you into a population (i.e. what region your relatives likely came from)

Genetic drift

is the change in the frequency of a gene variant (allele) in a population due to random (sub) sampling.

With subsampling phenomenon continue to reduce genetic diversity

People that migrated farthest away from Africa, you will continue to get reduced genetic variation, not a good thing, turns out having a great deal of genetic diversity is really good for preventing disease

Lineage-based versus Admixture testing approaches

- The genetic markers on mitochondrial DNA (SNPs) and Y-chromosomes (microsatellite marks and SNPs) can be used for the lineage-based approach. To trace the maternal and paternal lineages, respectively

- Since many ancient SNPs are shared across populations, one can use these for admixture testing to determine the ancestry of a person; this is done by determining the relative percentages of different SNPS in the genome associated with different ancestral regions

- In summary, different populations will have different SNP signatures (as well as microstate markers) and the origins and ancestry of an individual can be assessed by identifying the specific markers in that individual to all other individuals who have been "genotyped"

Another way to look at genetic drift/subsampling in the Domestication Bottleneck

- Certain wild plants or animals were selected from the environment and then bred, this led to on bottleneck

- Then, over time modern scientific plant an animal breeding aimed at crop/animal improvement (say a fungus-resistant corn) created a second bottleneck

- This had led to loss of genetic variation

Admixture Testing: Parts of nine ancestral regions are the basis for a population's genome

Relative percentages in your genome are then calculated and compared to the population-specific percentages that have been assessed for the different regions of the world:

- Mediterranean

- Northern European

- Southwest Asian

- Sub-Saharan African

- Southern African

- Northeast Asian

- Southeast Asian

- Native American

- Oceanian

Disease Implications of Genetic Drift

- As we have discussed, if a small group of individuals left a larger population (say, the original Africa) they would bring with them only limited diversity, thus, the new population would have less diversity as a whole than the original population

- Therefore, the greatest diversity to be found is in Africa whereas some of the least amount of diversity is seen in the Americas

How the body fights off infection

- Innate immune system (nonspecific response, no memory, found in basically all forms of life)

- Adaptive immune system

Lupus

Autoimmune disease in which immune system mistakenly attacks healthy tissue. Can be mild to severe, and common symptoms include painful, swollen joints; fever, chest pain, hair loss, muscle pains, swollen lymph nodes, fatigue, and red rashes

Oftentimes (but not always) due to anti-nuclear antibodies (e.g. anti-dsDNA) that create an inflammatory response. Treatments include administration of corticosteroids, immunosuppressants, methotrexate among other things (reduce activity of immune system)

Can involve the kidneys; lupus nephritis is an inflammation of the kidneys such that the glomeruli (filtration units of the kidney) become inflamed (glomerulonephritis)

Kidney failure can result.

Lungs and eyes can also be affected. Patients have increased risk of cardiovascular disease (most common cause of death), shortened lifespan

When comparing DNA sequences, we are most closely related to which of the following?

Neanderthals

Which of the following terms is not directly related to the others?

Admixture testing

In order to identify gene variants inherited from Neanderthals that contribute to disease in modern humans, what type of study/analysis is performed?

Genome-wide association study

A domestic bottleneck is an example of which of the following?

Genetic drift

The greatest genetic diversity is found where?

Africa

Low haplotype heterozygosity means what?

Decreased genetic diversity

The evolution of humans started where?

Africa

Which of the following is true about admixture testing?

Looks at markers on all chromosomes

For the Genographic Project, how many ancestral regions are considered when performing admixture testing?

Nine

Which of the following disease associations have been found by analyzing Neanderthal DNA? (SELECT ALL THAT APPLY)

Tobacco use

Diabetes

Celiac Disease

Depression

Skin lesions

Which of the following is NOT a characteristic of Sotos Syndrome?

Lung congestion

What is the term used to denote genes for which one single copy is insufficient to prevent disease?

Haploinsufficiency

The encoded protein of the gene that is mutated in Sotos Syndrome primarily modifies what proteins?

Histones

What kind of inheritance pattern is seen with Sotos Syndrome?

Autosomal dominant

Which of the following foods has anti-inflammatory properties?

Strawberries

What percentage of the genome is made up of protein-coding exons?

~2%

The technique to enrich for and sequence all exons in the genome is called what?

Whole exome sequencing

In one run, the Illumina HiSeq system can sequence how many bases of DNA?

One billion

What anti-cancer drug compromises the enzymatic pathway that is disrupted in Miller Syndrome?

Methotrexate

True or False: A chromosomal inversion is considered a copy number variant.

False

The mesoderm gives rise to all of the following, except what?

Epidermal cells of the skin

What is the term for a CNV deletion "uncovering" a recessive mutation, thereby causing a genetic disorder?

Pseudodominance

The lower layer of the trilaminar disk is made up of what?

Endoderm

A mutation that is present in the child but not in either parent is what kind of mutation?

de novo mutation

The process that produces copy number variants is called what?

Non-allelic homologous recombination

True or False: The endoderm gives rise to the gut.

True

A morula is made up of how many cells?

32

The fertilized egg is referred to as a what?

Zygote

True or False: The notochord induces a change in the ectoderm.

True

When performing aCGH, less DNA fluorescence of a region of a chromosome in a case compared to a control denotes what?

A deletion

What other abnormality commonly occurs in spina bifida? PICK THE BEST ANSWER

Hydrocephalus

The notochord signals the ectoderm to induce the formation of what structure?

Neural plate

Spina bifida with myelomeningocele has what material in the protruding sac?

Both fluid and nerve tissue

Select which pathway is not associated with neural tube defects.

Cytokine activation pathway

Spina bifida with myelomeningocele occurs at what region of the spine?

Lumbar/sacral regions

True or False: The cranial neuropore closes after the caudal neuropore.

False

The meninges are made up of how many membranes?

Three

The depressed midregion of the forming neural tube is called what?

Neural groove

Our spina bifida special guest on Tuesday is able to move around town with the assistance of what?

Leg braces

The tips of the neural folds give rise to what cell type?

Neural crest cells

As discussed in class, the simultaneous presence of two chronic diseases or conditions is referred to as what?

Comorbidity

True or False: GABA is an excitatory neurotransmitter.

False

Which of the following is NOT considered an Autism Spectrum Disorder?

Epilepsy

The actress Daryl Hannah to this day still exhibits a characteristic of ASD by doing what?

Rocking back and forth

Choose which of the following signaling pathways in the basal ganglia is INCORRECT:

Substantia nigra to motor cortex to thalamus

True or False: All individuals with ASD have the same intellectual disabilities.

False

Which of the following is/are key sign(s) of an autism spectrum disorder? (PICK ALL THAT APPLY)

Communication and social issues

Behavioral Issues

Inappropriate responses to environmental stimuli

Which of the following are functional pathways commonly mutated in autism spectrum disorders? (PICK ALL THAT APPLY)

Cell proliferation

Regulation of gene expression

Protein synthesis and degradation

Synaptic functions

30% of ASD patients also suffer from what condition?

Epilepsy

When dopaminergic neurons of the substantia nigra die, what is the end result? (SELECT ALL THAT APPLY)

Repression of the globus pallidus is decreased.

Repression of the thalamus is increased.