| Author | Question | Answer | |
| Fagundes et al | Question? | Are Native American haplogroups part of a founding population (explaining whether North America was settled by a single or multiple migrations) and what was the path and era of the migration(s) across the Americas? | |
|---|---|---|---|
| Importance? | Human history. | ||
| Strategy? | Analysis of haplogroups within mitochondrial genomes, correlated to geological events (glacier melting), weather changes (ice age) and archaeologial finds. | ||
| Results? | North America was settled by a single founding population which migrated along a Pacific coastal route from Asia and throgh | ||
| Interpretation? | |||
| Next Step? | |||
| Hanna et al | Question? | Can induced pluripotent stem cells stimulated into hematopoietic progenitors and transgenic for a healthy β chain allele, resolve a sickle cell anemia mouse model? | |
| Importance? | Possible future stem cell treatments of patients with sickle cell anemia. | ||
| Strategy? | Induce epithelial cells into pluripotency, gene target to replace an hβs allele, stimulate into hematopoietic progenitor cells and transplant into irradiated mice. Then examined red blood cells via direct microscopy (for evidence of sickling), PCR of hβs and hβa DNA and electrophoresis of hemoglobin proteins to determine if hemoglobin A is being expressed. | ||
| Results? | Via every manner of examination, the mice apparently had functional red blood cells with hemoglobin A and not only hemoglobin S post-treatment. | ||
| Interpretation? | The presence of hemoglobin A — and the lack of sickling, the direct phenotype — indicates a successful experiment. | ||
| Next Step? | Developing similar iPS treatments for recessive thalassemias, and possibly even for other kinds of genetic diseases. | ||
| Kagami et al | Question? | What mutations in imprinted Chromosome 14 regions can lead to phenotypes resembling maternal or paternal upd(14)? | |
| Importance? | Identifying genes and their products involved in the maternal and paternal upd(14) phenotypes opens up potential for gene therapies. | ||
| Strategy? | Identify individuals with phenotypes resembling paternal and maternal upd(14) but who are not actually uniparentally disomic for Chromosome 14. Examine the imprinted regions within Chromosome 14 for deletions, variations, epimutations (methylation analysis) and FISH analysis. | ||
| Results? | Found mutations of maternally expressed genes (MEGs) MEG3, RTL1as and MEG8 for most patients with a phenotype resembling paternal upd(14). Found mutations of paternally expressed genes (PEGs) DLK1 alone, or DLK1 and RTL1 for patients with a phenotype resembling maternal upd(14). | ||
| Interpretation? | Overexpression or underexpression of genes in imprinted regions of Chromosome 14 lead to a phenotype resembling maternal or paternal upd(14). | ||
| Next Step? | Knocking out and knocking in of DLK1 and RTL1, and MEG3, RTL1as and MEG3, to simulate overexpression and underexpression of the genes potentially leading to maternal and paternal upd(14) phenotypes. | ||
| DMR = Differentially Methylated Region. Epimutations = Epimutations are stable (affect progency cells) changes in gene expression not involving DNA sequence changes. |
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| Moller et al | Question? | Does DYRK1A play a role in Down Syndrome? | |
| Importance? | Global genetic disease. | ||
| Strategy? | Examine non-Down-Syndrome patients with Down Syndrome similar phenotype. | ||
| Results? | Patients had truncation of DYRK1A gene. | ||
| Interpretation? | Down Syndrome patients have extra DYRK1A gene. Patients in this study had truncated DYRK1A gene. DYRK1A gene expression must be tightly regulated or microcephaly, low weight, low height and possibly phalangeal defects can occur at varying intensities. Overexpression or underexpression of DYRK1A gene both lead to disease phenotype. | ||
| Next Step? | Create mouse models of overexpression (transgenic for constitutive DYRK1A promoter) or undexpression (knockout of DYRK1A) to examine if DYRK1A gene alone is responsible for the disease phenotype. | ||
