Korean University Bioscience Past Paper PDF

# 생명과학의 세계 The World of Bioscience Korea University ## 주차 03 ### 01. 아들의 지능은 엄마가 결정한다? (1) #### 01. CHILDREN INHERIT THEIR INTELLIGENCE FROM THEIR MOTHER NOT THEIR FATHER? (1) ##### 학습목표 1. Can understand the concept of de novo mutation. 2. Can understand the concept o...

# 생명과학의 세계 The World of Bioscience Korea University ## 주차 03 ### 01. 아들의 지능은 엄마가 결정한다? (1) #### 01. CHILDREN INHERIT THEIR INTELLIGENCE FROM THEIR MOTHER NOT THEIR FATHER? (1) ##### 학습목표 1. Can understand the concept of de novo mutation. 2. Can understand the concept of genetic variants. ##### 학습내용 1. De novo variant 2. Genetic variants in our DNA ### New mutation from sperm A tree diagram is shown. - The top node shows the "Primordal male germ cell". - The tree branches several times by "mitotic divisions'" with a total of 30 divisions. - Eventually, the tree ends in two smaller trees, both labelled "spermatids" which then form "Spermatozoa". ### New mutation from egg - A tree diagram is shown. - The top node shows the "Primordal female germ cell". - The tree branches several times by "mitotic divisions" with a total of 22 divisions. - Eventually, the tree ends in three nodes: "First polar body", "Second polar body" and "Zygote". ### De novo variants - "De novo" means "newly occurring". - "Mutation" and "variant" have the same meaning, but “variants” is a more general term. - De novo variants are those that occur newly in the sperm from the father or the egg from the mother. - We all have some number of de novo variants, averaging around 70 variants. ### Achondroplasia - A picture shows a boy with Achondroplasia and lists the characteristics: Macrocephaly, Trident Configuration of the hand, Shortening of the Limbs, Bowed Legs, Short Foot and Toes. - Achondroplasia is the most common skeletal dysplasia found in humans, accounting for 90% of cases of disproportionate short stature. - It is caused by a variant of the fibroblast growth factor receptor 3 (FGFR3) and has an autosomal dominant inheritance. - The characteristic phenotype includes rhizomelic shortening of the extremities, and affected individuals have an increased risk of mortality in early childhood and suffer from spinal pathologies into adulthood. ### Achondroplasia - It is primarily caused by a variant in the FGFR3 gene, which encodes a fibroblast growth factor receptor. FGFR3 plays a crucial role in regulating bone growth during development. - The G380R mutation is a specific point mutation within the FGFR3 gene. It results from a substitution of the amino acid glycine (G) with arginine (R) at position 380. - The G380R mutation leads to a constitutively active FGFR3 receptor. This constant activation disrupts the normal inhibitory function of FGFR3, leading to excessive inhibition of bone growth. ### Achondroplasia - An illustration shows a boy with Achondroplasia with a caption describing the features. - The caption describes the features of the boy in the picture. - an arrow is drawn pointing to the right to "Achondroplasia" - The cause of Achondroplasia is indicated with another arrow pointing to the left from "Achondroplasia" to "Cause" and labelled "FGFR3 G380R". ### Achondroplasia - A diagram shows a section of DNA with the label "FGFR3 Mutation". - The diagram is labelled as "Achondroplasia" on top and "Cause of Dwarfism" on the right. - An "X" sign is shown over a picture of a molecule labelled "FGF". - The central dogma is depicted: DNA --> RNA --> Protein with each stage labelled. - The caption describes the process of "FGFR3 mutation" leading to a "FGFR3 protein" which is "constantly active" causing bone growth to "slows". - An arrow points to the right from "FGFR3 G380R" to "Achondroplasia". - Below the arrow is a section labelled as "central dogma" which is linked to the diagram. ### So, variant is "allele" - On these days, however, allele is a variant that changes in your DNA sequence. - DNA consists of A, T, G, and C nucleotides. - If A is changed to T, it is called "variant". - If G is changed to A, it is called "variant". - Allele is “대립유전자” and is not the same as gene "유전자”. - Gene (유전자) encodes protein. - Allele is a change in DNA sequence. ### So, variant is "allele" - Synonymous/silent – Due to redundancies in the genetic code, many nucleotide changes will not change the amino acid sequence, for example, a GCT to GCC change would still encode an alanine. - Missense - This change results in a change in amino acid, for example, ACC threonine to AAC asparagine. - Nonsense - These turn a coding codon, such as GGA glycine, to a stop codon, e.g. TGA. This will result in a truncated protein, which may or may not be subject to nonsense-mediated decay depending on where in the peptide it occurs. - A table shows several codons and their amino acid outcomes. The table is divided into three sections for each codon: - DNA level - mRNA level - Protein level - The table shows several types of mutations: - No mutation - Silent - Nonsense - Missense (conservative - Missense (non-conservative - The table also shows the molecular structure of the amino acid for each type. ### Variants/mutations are harmful? - A screenshot of a Science article is shown. - The title of the screenshot is "A systematic survey of loss-of-function variants in human protein-coding genes". - The screenshot describes research into genetic variants and their relation to the human genome. ### We have 70 de novo variants but are they all doing something? - If de novo variants act like FGFR3 G380R, we are like Wolverine from X-Men. Variants do not work like this. Indeed, most variants are neural so we, human, do not vary trait much. - Because most variants are neutral we can transmit our variants to the next generation. - A very few de novo variants are under natural selection – it's very unlikely. Likewise, a very few de novo variants are advantageous to selection. - Variants are neutral so can be segregated in current humans. ### We have 70 de novo variants but are they all doing something? - A diagram is shown illustrating the concept of de novo variants. - The diagram follows the lineage: - You - Your child - Your grandchild - Your great-grandchild - Each stage in the lineage inherits 70 de novo variants from the previous stage, and adds another 70 de novo variants. - Eventually, "so many variants" are present in the great-grandchild. - Most variants are neutral and no or very marginal impact on traits so it cannot be subject to natural selection. ### Out of Africa - A diagram is shown with two scales: - Time: 0.08 to 0.15 Myr ago, 0.42 to 0.84 Myr ago and 1.7 Myr ago. - Location: Africa, S. Europe, N. Europe, S. Asia, N. Asia, Pacific and Americas. - Several arrows are drawn connecting the time and location scales, showing the spread of humans around the world over time. ### The Long History of Human Evolution: A Genome of variants - A tree diagram representing human genealogy is shown. - Human evolution is marked by a long and complex history. - Over millions of years, various factors have contributed to the accumulation of variants in the human genome. - As generations pass, variants accumulate in the genome. - Most variants are harmless, but some can lead to genetic diversity and adaptations. ### Polygenic Model - Many variants can make genetic diversity. - Polygenic: the prefix “poly-" means “many” or “multiple,” and “genic” is related to “allele (variant)”. - It refers to a trait or characteristic that is influenced by multiple alleles (variants). - Polygenic results in genetic diversity that we have very different to each other. When you look at a certain phenotype, there is a spectrum for its value. ### Polygenic Model - An illustration is shown with the caption "Number of individuals" on the left axis and "Height in inches" on the bottom axes. - The illustration depicts a normal distribution curve of height. ### Inconsistent with Mendel's law? - Variants seem to contribute to genetic diversity and traits. There is a spectrum of the phenotype. - The phenotype does not exist in Mendelian ratio, Height is not 3:1 ratio in human. ### 학습정리 - Phenotypic variation is sourced by de novo variants in every generation. - A few variants greatly contribute to traits and disorders, but most variants are neural and are segregated to the next generation. - Genetic variants in our DNA are referred to as “alleles.” ### 출처 및 참고문헌 - [참고문헌] Templeton, “Out of Africa again and again”, Nature, 2002 Mar 7:416(6876):45-51. - [출처01] Crow, “The origins, patterns and implications of human spontaneous mutation”, Nat Rev Genet. 2000 Oct;1(1):40-7 - [출처02] NCBI, https://www.ncbi.nlm.nih.gov/books/NBK559263 - [출처03] SDG Resource Centre, Osmosis and the National Organization for Rare Diseases(NORD), “Rare Disease Education: Achondroplasia”, https://sdgresources.relx.com/features/rare-disease-education-achondroplasia - [출처04] Mendel, G. “Versuche über Plflanzen-hybriden.”, Verhandlungen des naturforschenden Vereines in Brünn, Bd. IV für das Jahr 1865, Abhand-lungen, 3-47 (1866) (Bateson translation) - [출처05] Wikimedia, https://commons.wikimedia.org/wiki/File:Different_Types_of_Mutations.png - [출처06] MacArtur et al., “A systematic survey of loss-of-function variants in human protein-coding genes”, Science, 2012 Feb 17:335(6070):823-8 - [출처07] Templeton, “Out of Africa again and again”, Nature, 2002 Mar 7:416(6876):45-51. - [출처08] Albers & McVean, “Dating genomic variants and shared ancestry in population-scale sequencing data”, PLoS Biology, 2020 Jan; 18(1): e3000586 - [출처09] Asking About Life (2nd Edition; 2001) by Tobin & Dusheck, Harcourt Inc.