Genetic Diseases Leigh Syndrome Gene Editing by Sam

Genetic Diseases Leigh Syndrome Gene Editing by Sam Elkinson 1

Genetic Mutations n n n Medical conditions result from a faulty version of a gene. Genetic mutations occur when DNA changes and this can be caused by mutagenic agents such as radiation. Mutations also occurs when DNA fails to be copied accurately when a cell divides. 2

Passing on Mutations n n Some medical conditions are directly caused by a mutation in a single gene that may have been passed on to a child through his or her parents Genetic conditions can be inherited in 3 main ways 3

Autosomal Recessive Inheritance 4

Examples of autosomal recessive genetic conditions n n Cystic fibrosis Sickle cell anaemia Thalassaemia Tay-sachs disease 5

Autosomal dominant inheritance 6

Examples of these genetic conditions n n n Tuberous sclerosis Huntington’s disease Polycystic kidney disease 7

X-linked inheritance n n n Characteristic is said to be sex-linked when the allele that codes for it is located on a sex chromosome. Y chromosome much smaller than X chromosome – carries fewer genes. Males only have one X chromosome, so only have one allele for sex-linked genes. 8

Examples of X-linked inheritance conditions n n Colour blindness Haemophilia 9

New Mutations n n Some genetic mutations are not always inherited Mutation can occur when a sperm or egg is made, when a sperm fertilises an egg or when cells divide after fertilisation. 10

Chromosomal conditions Abnormality in a person’s chromosomes – having too many or too few chromosomes, rather than the normal 23 pairs Conditions: Down’s syndrome, Edward’s syndrome, Patau’s syndrome, Turner syndrome and Klinefelter’s syndrome n 11

Influence of the environment n Health conditions are caused by genes and environmental factors – lifestyle factors such as diet and exercise e. g. coronary heart disease, obesity, diabetes 12

What is Leigh Syndrome? q q The disease is named after Archibald Denis Leigh, a British neuropsychiatrist who first described the condition in 1951. Leigh's disease is a rare inherited neurometabolic disorder that affects the central nervous system. This progressive disorder begins in infants between the ages of three months and two years. The prevalence of Leigh syndrome has been estimated at 1 in 36, 000 -40, 000 live births. The condition is more common in certain populations. This includes regions of Quebec, Canada and regions of the Faroe Islands. 13

Mostly autosomal recessive inheritance 20% mitochondrial inheritance Small number X-linked inheritance 14

Impacts of Leigh Syndrome DIARRHOEA DIFFICULTY SWALLOWING LOSS OF HEAD CONTROL SEIZURES CONTINUOUS CRYING VOMITING POOR SUCKING ABILITY DIFFICULTY BREATHING 15

Severe muscle and movement problem Weak muscle tone Problems with movement and balance Inability to gain weight and grow Involuntary muscle contractions Episodes of lactic acidosis Impairs kidney and respiratory function 16

Leigh Syndrome Diagnosis and Assessment q q Magnetic resonance imaging (MRI) Computed tomography (CT) - scans of the brain may reveal abnormal areas in certain parts of the brain Blood tests – shows ketoacidosis (formed from breakdown of fatty acids and amino acids). CSF = cerebrospinal fluid – tests on fluid surrounding the brain and spinal cord. 17

What treatment / therapies exist for Leigh Syndrome? There has been no specific treatment for Leigh disease in the past. q Dietary treatment and vitamin treatment has been tried but with very little success. q However…. q 18

Three-person baby license q q Fortunately the three-person baby license has recently been granted, allowing women with mitochondrial DNA mutations to have the opportunity to have more reproductive choice. This may not be a direct treatment for someone with Leigh syndrome however it prevents Leigh syndrome from being passed down generations. Many people are in favour of this procedure as it could help increase the chance of survival and improve a child’s quality of life. Other views are that the procedure is unethical as it is similar to producing designer babies and ‘playing god’. 19

Three-person baby licence has been granted q q q In mid-March, doctors in Newcastle were given the first UK license to create babies from 2 women and one man. It is an advanced form of IVF and can be used to prevent children dying from genetic diseases, including Leigh syndrome. This three-person baby technique is only allowed to take place in cases where the risk of a child developing mitochondrial disease is very high. Aim of procedure: to get healthy mitochondria from the donor. As mitochondria have DNA of their own, the resulting baby will have DNA from three people. 20

Three-person baby licence has been granted Dr John Zhang – part of USA team who performed procedure in Mexico, as there wasn’t a licence in America. So far reports are that the baby is doing well. 21

Why is it importance to know about Leigh Syndrome? q q After the three-person baby procedure, if successful, it could open new doors to people suffering from the condition. This could give them more hope for the future, increasing their quality of life dramatically. 22

Gene editing n https: //www. youtube. com/watch? v= av. M 1 Yg 5 o. Eu 0 23

Gene editing n This is a potential game-changer as it implies that we may be able to change the genetic makeup of entire generations on a permanent basis. 24

Is gene editing ethical? § § Gene editing holds the key to preventing or treating debilitating genetic diseases, giving hope to millions of people around the world. Yet the same technology could unlock the path to designing our future children, enhancing their genome by selecting desirable traits such as height, eye colour, and intelligence. 25

Ethical issues • • • Eugenics is a set of beliefs and practices that aims at improving the genetic quality of a human population. Eugenics refers to both the selection of positive traits (positive eugenics) and the removal of diseases or traits viewed negatively (negative eugenics). Eugenics in either form is concerning because it could be used to reinforce prejudice and narrow definitions of normality in our societies. 26

n https: //www. youtube. com/watch? v= 06 Jq 2 i. XL_tc 27

What sources did I use? q q q BBC News Genetic Home Reference NORD – National Organisation of Rare Disorders orpha. net medicinenet. com biomedcentral. com 28