Presentation on theme: "Understanding patterns of inheritance"— Presentation transcript:
1 Understanding patterns of inheritance This presentation builds on session 1 exploring patterns of inheritance
2 Patterns of inheritance The objectives of this presentation are to:Understand how genes are inheritedUnderstand the differences between the inheritance patterns associated with Autosomal dominant, Autosomal recessive, X-linked recessive and chromosomal abnormalitiesUnderstand that the environment can impact on some common complex conditionsAutosomes refer to the first 22 pairs of chromosomes
3 So how are genes passed on from parent to child? ChromosomeGeneGenes in the cell nucleus are physically located on 23 pairs of chromosomesOne set of 23 chromosomes is inherited from each parentTherefore, of each pair of genes, one is inherited from a person’s mother, and one from their fatherDiagram showing just one pair of the 23 pairs of chromosomes in the cell nucleus. The location of one of the genes on this chromosome is shown.For example: ear lobe structure attached or unattached would be located on the same position on the same number chromosome from Mum and Dad
4 Classification of genetic disorders Single Gene DisordersMaleAlterations in single genesMultifactorial diseases+ environmentVariants in genesSingle Gene – Red represents altered gene in 1st top left pair of Chromosomes 1 altered and 1 unaltered – individual may or may not be affected by this (unless this is a dominant alteration)2nd pair shows both genes altered – individual will be affected3rd pair show the sex chromosomes with one alteration but as this is a male XY and the alteration is on the X the male will be affected as there is no counterbalance on the Y chromosomeMultifactoral – Genes rarely act alone e.g. Height they may have the gene for tall but if malnourished may be short. Changes in both genes can have different variants for example the gene for skin colour not just black and white but shades and environment Sun adding further colour or damage.Chromosomal – Session 1 reminder extra chromosomes plus insertions and deletionsChromosome disordersChromosomal imbalance
5 Single gene disordersSome medical conditions are caused by a change in just one or both copies of a particular pair of genes. These are called “single gene disorders”.The three common types of single gene disorders are called:Autosomal dominantAutosomal recessiveX-linkedAD – always expresses itselfAR - only expresses in the absence of dominant unaltered gene – healthy carrierX – genes found on X chromosomes
6 Homozygotes must have two copies of the altered gene to be affected DominantThese individuals are called Heterozygotes with one copy of the altered gene they are affectedRecessiveHomozygotes must have two copies of the altered gene to be affectedHetero means ‘different’, homo means ‘same’Homozygotes – received an affected chromosome from each parent who may have been healthy unaffected carriersX-linked – always affected as they don’t have an X to balance the affected chromosomeMaleX-linked recessiveMales with an altered gene on the X-chromosome are always affected
7 Examples of Autosomal Dominant Conditions Autosomal dominant inheritanceExamples of Autosomal Dominant ConditionsHuntington diseaseNeurofibromatosis type 1Marfan syndromeFamilial hypercholesterolemiaFamilial Adenomatous Polyposis (FAP)Prader-williSee NGEDC website ‘Search Conditions’ for further information on each of these conditions
9 Autosomal dominant inheritance ParentsGametesThese slides show how and affected dominant gene is inherited by each conception. That this ‘chance’ occurs at each conception is a very important point as a miss-conception “ We have 1 affected child so the next one in a 50:50 chance will be unaffected” is a fairly common occurrence. The same probability is present for each child conceived and is not affected by previous pregnancies.
10 Autosomal dominant inheritance ParentsGametesAtconceptionEnsuring that the students and therefore the parents understand ‘chance’ is key they need to use what is best for the patient50:50 or 2 in 4 or 50%UnaffectedAffectedAffected
11 Examples of Autosomal recessive conditions Autosomal recessive inheritanceExamples of Autosomal recessive conditionsSickle Cell diseaseCystic fibrosisBatten DiseaseCongenital deafnessPhenylketonuria (PKU)Spinal muscular atrophyRecessive blindnessMaple syrup urine diseaseNeed both genes in an altered state to show the condition.See NGEDC website ‘Search Conditions’ for further information on each of these conditions
14 AUTOSOMAL RECESSIVE INHERITANCE ParentsParent who are carriers for the same autosomal recessive condition have one copy of the usual form of the gene and one copy of an altered gene of the particular pairThe parents are usually healthy carriersThis is not unusual to be a carrier, so many individuals are unaware of their carrier status.For example 1 in every 12 people in the UK are carriers for the cystic fibrosis gene.
15 AUTOSOMAL RECESSIVE INHERITANCE ParentsSperm/EggsA parent who is a carrier passes on either the usual geneThe other parent who is also a carrier for the same condition passes on either the usual gene or the altered gene into his/her eggs or spermor the altered gene into the eggs or sperm
16 AUTOSOMAL RECESSIVE INHERITANCE ParentsSperm/EggsUnaffected (carrier)Unaffected (carrier)The way to explain ‘chance’ this to the patient or parent is 1 in 4 or 25% chance of being affected or 75% chance of being unaffected 50% chance of being a carrierUnaffectedAffected
17 Examples of X-Linked Recessive Conditions X-Linked recessive inheritanceExamples of X-Linked Recessive ConditionsFragile X syndromeHaemophiliaDuchenne muscular dystrophy (DMD) (Becker BMD)Fabry diseaseRetinitis pigmentosaAlport syndromeHunter syndromeOcular albinismAdrenoleucodystrophy.If men have the altered gene they are generally affected. Women with the altered gene may be affected to a varying degree dependant on the activity of the normal gene.
19 X-linked recessive inheritance MaleFemaleXYXXOne copy of an altered gene on the X chromosome causes the disease in a male.An altered copy on one of the X chromosome pair causes carrier status in a female.Female – and may also be affected but this may be reduced depending on the gene involved
20 Y X Parents Gametes X X (Unaffected) (Carrier) Father Mother X-linked inheritance where the mother is a carrierFatherMotherYXParents(Unaffected)(Carrier)GametesXXAtconceptionThe risk of being affected is dependant on if at conception it is a male or femaleDaughterDaughter (Carrier)Son (Affected)Son
21 Polygeneic Inheritance Single gene disorders are quite rareSingle gene disorders either give risk to a condition or they don’tMost traits are Polygenic’ i.e. 1 trait coded by a number of altered and unaltered genes working togetherThe additive effects of 2 or more genes leading to a continuous variation rather than the either /or of a single gene
22 Common Polygenic Disorders Alzheimer'sDiabetesCancerEczema
23 Multifactorial inheritance Inheritance controlled by many genes plus the effects of the environmentAdult onset disorders Diabetes mellitus Epilepsy Glaucoma Hypertension Ischaemic heart disease Manic depression SchizophreniaCongenital malformations Cleft lip/palate Congenital hip dislocation Congenital heart defects Neural tube defects Pyloric stenosis TalipesGenes rarely act alone and both single and polygenic can be multifactoral
24 Rare Genetics simple Unifactorial High recurrence rate The contributions of genetic and environmental factors to human diseasesGENETIC ENVIRONMENTALDuchennemuscular dystrophyHaemophiliaOsteogenesis imperfectaClub foot Pyloric stenosis Dislocation of hipPeptic ulcer DiabetesTuberculosisPhenylketonuria GalactosaemiaSpina bifida Ischaemic heart disease Ankylosing spondylitisScurvy100% genetic100%EnvironmentalRare Genetics simple Unifactorial High recurrence rateCommon Genetics complex Multifactorial Low recurrence rate
25 MultifactorialExamples include some cases of cleft lip and palate; neural tube defects; diabetes and hypertensionCaused by a combination of genetic predisposition and environmental influencesPattern – more affected people in family than expected from incidence in population but doesn’t fit dominant, recessive or X-linked inheritance patternsOther patterns of InheritanceCleft lip and palate is an example of a condition which may have a genetic factor but can also have environmental causes. For example, certain drugs used to treat epilepsy are associated with an increased incidence of cleft lipGenetic factors underlie many common diseases such as cancer, heart disease and diabetesWhen there is significant family history, monitoring and preventative regimens can be offered. Genetic testing is currently very limited but much research is underway
26 Chromosomal abnormalities Some medical conditions are caused abnormalities in chromosome number or structure.Chromosome abnormalities was covered in “DNA, genes and chromosomes” presentation in lesson 1. The next 3 slides provides a refresher of the previous lesson.
27 Chromosome anomaliesCause their effects by altering the amounts of products of the genes involved.Three copies of genes (trisomies)= 1.5 times normal amount.One copy of genes (deletions)= 0.5 times normal amount.Altered amounts may cause anomalies directly or may alter the balance of genes acting in a pathway.