Hi, my name is Masako Ueda. I'm a clinical geneticist and also an endocrinologist. So I really thank the endocrinology, endocrine society for allowing me to make this program so that this program will facilitate endocrinologists and other healthcare professionals to become familiar with the field of clinical genetics so that clinical genetics testing can be integrated into their own practice. So for this program, learning objectives are review basic terms in genetics and clinical genetics. When should you suspect a genetic disorder? So I'm going to try to explain that during the case that I'm going to present, I'm going to be presenting and why and what types of genetic testing should you order and what are implications of genetic testing and how do you interpret clinical genetic test results. So as you know, Mendel has played a great part in our discovery of DNA ultimately and his observation of plant garden, plant key was very instrumental in learning about hereditary material. So Fredrik Miescher was the first person who identified the presence of DNA in 1860 and Rosalind Franklin discovered the structure of DNA by X-ray crystallography and she laid the foundation for the James Watson and Francis Creek to discover the double helix structure of deoxyribonucleic acid, which is a DNA in 1953. So the Hemping project was initiated in 1990 and the completion was 2003. At the time we thought that, oh, we'll know everything about human genetics when we know the human genome sequencing wrong. We at the time started just learning about human genetics or genome. So from then there are numerous project has initiated and we're still learning a lot about human genome. So I wanted to just briefly introduce you to clinical genetic field of medicine, which focuses on inherited disorders. We do medical practice guided by genetic principles, clinical care of individuals with genetic disorders, and diagnose using variety of molecular and biochemical analysis and management based on genetics and biochemical findings from these testing. And genetic counseling especially is a big part of clinical genetics. So genetic counselor do a lot in clinical genetics. They do pre, post genetic testing counseling, as well as family screening and family planning. So prenatal counseling is a big part of clinical genetics. So precision medicine has become a big word in medicine now. Medical care guided by integrating genomic lifestyle, environmental factors. So it's moving away from genetics, which is a study of specific genes and their roles and inheritance, investigation of the function and structure of individual genes. But now it's has moved on to the genomics, which is a relative new terms, study of all the genes in the genome and their interactions with each other, as well as within environment. So it includes the study of complex disorder, which are really complicated. And then part of it is development of novel therapeutics and technologies to study genomics. So current paradigm is patient comes to you, physician or healthcare providers. We examine patients, we do some workup, which include may include genetic testing. And once the genetic test results are received, then we make medical management plans. But future paradigm may be that genetic testing may already accompany the patient. So when they come to you, they may already have their data on genetics or genomics. Then you may do additional data according to the results, and then make management plans. So genetic testing may be more integrated into patients medical records. So I'm just going to go back to a little bit review basic genetics a little bit. So as you know, DNA is contained in nucleus, which is within the cell. And within cytoplasm, besides the nucleus, there are other organelles and including mitochondria, which has itself its own DNA. So DNA has a certain rules. And there are two purine adenine and guanine and pyrimidine, which were thymine and cytosine. So adenine and thymine always paired together. And guanine and cytosine always paired together. So they formed helical structure that way. And DNA is enclosed, tightly packed, protected by histones wrapped around, and it forms fibrous structure of nucleosome. And nucleosome forms fiber structure of chromatin. So two pairs of chromatin form chromosome. Typical gene is structure includes promoter area, whereas the RNA polymerase comes in and starts transcribing. And then primary RNA transcribes, then spliceosome comes in and splices out introns. And then mature mRNA does not include introns. And then 5' cap is placed as well as a poly-A tail that protects the mRNA from degradation and able to move out of this nucleus to cytoplasm. Once it's in the cytoplasm, ribosome and tRNA working together to translate the mRNA trinucleotide codons into proteins. So polypeptides forms and that forms the protein product. And they can go to wherever they need to go with their function. So let's talk about the human genome. It's a complete set of DNA sequences in the nucleus. So there are 22 pairs of autosomes and XY and XX sex chromosome. So 46 XX for female and 46 XY for male. And also in the mitochondria, mitoDNA, there's a double stranded circular DNA and special characteristic is it's only maternal inheritance. And each cell has multiple mitochondria and each mitochondrion has multiple mitoDNA. So there are two different types of DNA, but we'll just focus on the nuclear DNA for this session. And carrier type is the way that we identified all the chromosome in the individual. And it's not easy to do because I've done it with my chromosome that I couldn't find some of the chromosome because it's a banding identification and I couldn't find the banding. And some of the chromosome was really crooked. So I had difficult time finding all of my chromosome. Ultimately, I found them all. But all human beings have 99.9% identical DNA sequences across 3 billion nucleotide pairs. That means we are really, really very similar to each other. And if you look at the whole genome, only 30% is protein coded. So there is lots of other nucleotides that some do regulatory functions, other do we have no idea what they do. So we're still learning about our human genome as of this time. So 0.1% makes the difference, but those genetic variations makes us all different. Different hair color, different skin color, so forth, eye color, so forth. And single neuter variant is the most common type. And most common is like single nucleotide polymorphisms. It's very common. It's interspersed within the genome, maybe like a thousand nucleotide apart from each other. It is two or more variant forms of a specific DNA sequence present at a specific locus that are different among individuals in population. So that's like a marker for individuals. Some may have some functions, some may not have any function, but they make us all different. And copy number variances, also variation that makes us different. These are structural variations and result of deletions, insertions, and duplications. And mutation usually has a connotation of pathogenic variant, but it's just describes an event resulting in altered DNA sequence. So even myself, I'm going to be using a mutation as a pathogenic variant in some cases, but it's interchangeable, but then origin of the mutation itself is an event of altering DNA sequence, just to mention that.

clinical genetics

human genome

genetic testing

DNA structure

genetic variations