1. OI type I is selected against once the phenotype from the disease becomes apparent. In other words, natural selection acts upon the disease after reproduction age which is usually around twenties to thirties. Therefore, before menopause in women and age 60 in men, natural selection usually does not act upon the disease. During reproductive age, people with the genotype for OI type I has similar chances to everyone else for finding a mate since the phenotype for the disease is not apparent yet. Therefore, they could still pass on their genes to their offspring and remain in the population. Since the disease is autosomal dominant, only one dominant allele is required from the parent for the offspring to develop the disease. For example, if one affected heterozygous parent mates with a normal parent, half of their offspring will have the genotype for OI type I. The reason why the genes are remained in the population is because the phenotype is not expressed during reproductive age but rather later on in life. This enables them to reproduce as normal individuals and keeping in the gene in the gene pool.
2. In the essay, it states that the amino acid residues 328-429 from the chicken correspond exactly to those in humans. The similarity between the chicken and the human is most likely due to inheritance from a common ancestor. However, the sequence 430-447 in human is different from the chicken. According to the article, this difference might have been caused by divergence from a common ancestor more than 600 million years ago. There could have been a mutation in this segment of the gene that caused them to diverge at the location with the differences. Since this region of the genome sequence is similar, but in different species, they are considered as orthologous sequences.
3. The article stated that the repetitive structure of interstitial collagen genes is caused by serial duplication of the primordial 54-bp exon. There are two ways that this could have occurred. First, a possibility for duplication could have occurred by homologous exchange between the adjacent exons, mediated by chromosome pairing. Secondly, it could have been caused by non-homologous introns breaking and reuniting.
4. The process of transcription allows the RNA to form from the DNA. Translation is when the amino acids are formed from the codes of the RNA. After the proteins are translated, they fold according to the genetic code. By studying the folding of proteins, it is possible to compare the normal folding of proteins to the mis-folding of proteins to help understand the disease. By comparing the abnormal to the normal proteins, it is possible to pin-point the location of abnormality. Unlike OI type I, which is usually not acted upon by natural selection since the phenotype shows up in the later stage of life, the phenotype of type II shows up before birth. Since people with type II display the symptoms of osteogenesis imperfecta at throughout their life, natural selection acts against them which make it difficult for them to survive to reproductive age.
5. The reason why this method works is because viral vectors are the injection of viruses which contains genetic information. Basically, the idea is exposing a cell with a virus and once that virus infects that cell, it will block or silence production of a specific protein. In this case for OI, it is the production of proteins that makeup collagen fiber. If there was a regulatory gene mutation in a MSC, then the probability of MSC functioning properly is lowered because the proteins within the cell are changed. As a result, normal collagen are not formed by the MSC and will not help with OI.
