Biol 4355 - Genética Humana Capítulo 1 – Repaso de Genética UPR – Aguadilla JA Cardé, PhD

Objetivos Definir Genética y Genética Humana Repasar conceptos básicos de Genética Conocer aplicaciones de la Genética Repasar momentos claves en la historia de la Genética

Genética vs Genética Humana Estudio de la herencia, mecanismos hereditarios y sus variaciones Estudio de la herencia según se manifiesta en seres humanos. Incluye campos que se solapan entre si: genética, citogenética, genética molecular, genética bioquímica, genomas, genética del desarrollo, genética clínica, genética de poblaciones y consejería genética. Contesta preguntas sobre la naturaleza humana, entender enfermedades, desarrollar tratamientos efectivos para enfermedades, en fin comprender la genética en la vida humana.(Wikipedia- http://en.wikipedia.org/wiki/Human_genetics).

Genética Humana Estudio de la herencia según se manifiesta en seres humanos. Es importante para todo el mundo: estudiantes, profesores, profesionales, padres, hijos Es mas sobre las variaciones que sobre nuestras enfermedades, mas sobre lo común que sobre lo raro Antes la explicación era media oscura sobre conjuntos raros de síntomas, ahora es tema de conversación diaria Sirve de base de la ciencia médica Antes se hablaba de un gen para esto o aquello Hoy sabemos que varios los genes que interactúan entre si y con el ambiente para rasgos y condiciones (epigenesis)

Genética: Momentos Históricos Garden Peas Gregor Mendel, 1880s DNA structure Watson, Crick, Wilkins, Franklin, 1950s Human Genome Project NIH, DOE, Celera Corporation, 1990s-2000s

Genetics Is the study of inherited traits and their variation Is a life science that should not be confused with genealogy Figure 1.1 Is also an informational science that is having a huge societal impact

Genes Contain the instructions within the cells for protein production Genes are composed of deoxyribonucleic acid (DNA) Traits are produced by an interaction between the genes and their environment Figure 1.1

The Genome Is the complete set of genetic information for an organism It includes all of the genes present in an organism - And also DNA sequences that do not encode genes Genomics is a field that analyzes and compares genomes of different species

Levels of Genetics Niveles: 1. Instrucciones 2. Celulas Tejidos y Organos: Expresion 3. Epigenesis: Genes y Ambiente Niveles: 1. Instrucciones 2. Células Tejidos y Organos: Expresión 3. Epigenesis: Genes y Ambiente Figure 1.2

Deoxyribonucleic Acid (DNA) A double-stranded polymer consisting of a chain of nucleotides Deoxyribonucleotide components: - Phosphate - Sugar: Deoxyribose - Base: Adenine A Guanine G Thymine T Cytosine C The sequence of the bases code for the amino acid sequence in a protein El DNA son las instrucciones

Hélice Doble hebra Antiparalela Complementaria Reading1.1, Figure 1 Box, Figure 1 Hélice Doble hebra Antiparalela Complementaria Helice Doble hebra Antiparalela Complementaria Reading1.1, Figure 1

Ribonucleic Acid (RNA) A single stranded polymer of ribonucleotides Ribonucleotide components: - Phosphate - Sugar: Ribose - Base: Adenine A Guanine G Uracil U Cytosine C Exists in several types Uses information on DNA to construct proteins

Box, Figure 2 Expresion genetica Reading 1.1, Figure 2

The Human Genome Only 1.5% of our DNA encodes protein - About 20,325 protein-encoding genes in all Rest of the human genome includes highly repeated sequences with unknown functions Genes known to cause disorders or traits are cataloged in a database - Online Mendelian Inheritance in Man (OMIM) Proteomics is a field that studies the proteins made in a cell

Genes Alleles are variants of genes They form by mutation Mutations in sperm or egg cells are passed on to the next generation Mutations may be positive, negative, or neutral

Variations Polymorphisms are variations in the DNA sequence that occur in at least 1% of the population Single nucleotide polymorphisms (SNPs) are single base sites that differ among individuals - Can cause disease or act as genomic markers Resultan de Mutaciones

Variations Genome-wide association studies track SNP patterns among individuals who share a particular trait or disorder Gene expression profiling measures which genes are more or less active in particular cell types

Chromosomes Composed of DNA and protein Found in the nucleus of the cell Human somatic cells have 46 chromosomes - 22 pairs of autosomes - A pair of sex chromosomes - Females have two X chromosomes - Males have one X and a Y Sufren Duplicaciones Traslocaciones Deleciones Inversiones

Karyotype A chart displaying the chromosome pairs from largest to smallest Estudia la presencia o ausencia de cromosomas o sus partes Sondas con cromoforos para regiones especificas Figure 1.2 Figure 1.2

Nivel 1 – Informacion – Que tipo de informacion podemos obtener delDNA a distintos niveles Table 1.1

Cells A human body contains approximately 50-100 trillion cells - All cells except RBCs contain the same genome Differentiation causes cells to differ in appearance and function - Controlled by variation in gene expression Stem cells are less specialized and can become many different cell types 2do nivel Celulas Tejidos y Organos Resultan de la expresion diferencial del genoma

Levels of Biological Organization Segun pasamos del nivel de organizacion tambien cambia el patron de expresion diferencial del genoma en cada celula tejido u organo. Y organismo Figure 1.3 Figure 1.3

Table 1.2 4 tipos de tejidos basicos Conectivos Epitelial Muscular Nervioso Table 1.2

Individual The genotype of an individual refers to the alleles they carry The phenotype is the visible trait A dominant allele is expressed if the individual carries just one copy A recessive allele is only expressed if the individual carries two copies

The Family Individuals are genetically connected into families A pedigree is a diagram used to study traits in families - Can be used to trace multiple genes or genes with large environmental component - Will be discussed in detail in Chapter 4

A Population Is a group of interbreeding individuals The gene pool is the sum of all alleles in a population Evolution is the changing allelic frequencies in populations over time (Hardy-Weinberg)

Evolution Genome comparisons among species reveals evolutionary relationships - The more similar the sequences are, the more recent the divergence from a common ancestor 98% of human DNA sequences are shared with chimpanzees Humans share genes with mice, pufferfish, fruit flies, yeast, and even bacteria

Figure 1.4 Genes y genomas revelan nuestro lugar en el mundo. Toda la vida esta relacionada entre si Especies diferentes comparten un grupo bassico de genes Mientras mas similaridad en las secuencias , mas reciente la divergencia Mientras menos similaridad en las secuencias, mas lejano el punto de divergencia Figure 1.4

Mendelian vs. Multifactorial Traits Mendelian traits are determined by a single gene - Their recurrence is predicted based on Mendel’s laws Multifactorial traits are determined by one or more genes and the environment - Predicting their recurrence is much more difficult Most traits are multifactorial 3er nivel – Epigenesis. – Genes y Ambiente Genetica Mendeliana depende de un factor simple o en otras palabras un solo gen Predecible por leyes de Mendel Rasgos multifactoriales, uno o mas genes y EL AMBIENTE

Mendelian vs. Multifactorial Traits Polidactilia es mendeliana Color de pelo es multifactorial: 3 genes y ambiente, sol Osteoporosis – menopausia, varios genes mas fumar, falta de ejercicios de pesas y dieta pobre en calcio Figure 1.5

Genes and Disease Risk Genetic determinism is the idea that the expression of an inherited trait is inevitable This may be harmful or helpful, depending on its application - As part of a social policy, it is disastrous - Knowing genetic risks can help us make good choices La epigenesis o la capacidad modificante del ambiente contradice esto No somos nuestros genes o no esta en nuestros genes… Esto ignora el efecto del ambiente Por eso se puede decir q tienes un 45% de desarrollar tal condicion… hay varios factores de riesgos q deben coincidir y que tendran cierto tipo de peso

Applications of Genetics Genetics impacts many areas of our lives DNA profiling (DNA fingerprinting) looks at SNPs and short repeated DNA sequences - It has applications in: - Forensics - History and ancestry

Forensics Identification of victims of natural disasters or terrorist attacks (Baby 81) Matching the DNA of suspects to samples left at the crime scene Helping adopted individuals locate blood relatives

History and Ancestry DNA analysis can flesh out historical details - Revealing the offspring of Thomas Jefferson and Sally Hemmings - Revealing the origins of the Jewish Lemba of South Africa

History and Ancestry Figure 1.6 Figure 1.7 Figure 1.7

Health Care Pharmacogenomics is a field that identifies individual drug reactions based on genetics

Health Care Analysis of single-gene illnesses reveals many differences from other diseases

Health Care Diseases are increasingly being described in terms of gene expression patterns Tracking gene expression can reveal new information about diseases and show how diseases are related to each other - This is not obvious via traditional medicine

The Diseasome Combina enfermedades a expresion de genes algun gen particular puede estar sobre expresado o subexpresado en condiciones particulares asi relacionandolas Ejemplo Alz y corazon ambas comparten colesterol, asi drogas puesen ser redirigidas de una a otra condicion Estatina para colesterol probandose en Alz Figure 1.7

Genetic Testing and Treatment Tests to identify about 1,200 single-gene disorders have been available for years - Direct-to-consumer (DTC) genetic testing The Genetic Information Non-discrimination (GINA) act was passed in the US in 2008 Genome information is useful for developing treatment to genetic and infectious diseases

Agriculture Traditional agriculture is the controlled breeding of plants and animals Biotechnology is the use of organisms or their parts to produce goods and services Genetically-modified (GM) organisms have new genes or over- or under-express their own genes

Figure 1.9

Ecology Metagenomics is a field that involves sequencing all of the DNA in a habitat - The Sargasso Sea - The Human Microbiome Project Metagenomic studies may be used to reconstruct ecosystems

A Global Perspective Genetics and genomics are spawning technologies that may vastly improve the quality of life Human genome information has tremendous potential for the entire globe - Individual nations are using approaches that exploit their particular strengths

A Global Perspective Puerto Rico?