BSCI222 Lecture 11 10 10 13 missed L 10 Chapter 6 Pedigree Analysis Applications and Genetic Testing Do Pedigree analysis because Mendellian genetics don t work well with humans because small progeny can t do crosses have to use existing families etc o Have to gather data from many different generations instead in order to study the linkage among different genes o Many symbols for pedigrees PowerPoint slide Men are squares pointy women are circles round and unsure is diamond Individuals with a disease have their symbol fully filled in carrier only has part of their symbol filled Someone who s carrying the trait but not old enough to express it yet will have a line through their symbol Proband small p with arrow to the symbol is the first family member affected with the disease coming to the attention of genetics work backwards from there Deceased crossed through For twins have one line coming down from the parents like upside down Y with a small line connecting Y s legs if identical no line if non identical and question mark if unsure o Is the disease dominant or recessive Sex linked or autosome linked o Autosomal recessive similar frequencies in both sexes recessive so tends to skip generations and more likely to show up in the children of related parents assuming that the unrelated people marrying into the family are not carriers not a perfect assumption reason why first cousins are not allowed to marry o Autosomal dominant appears equally in males and females and observed in every generation Unaffected individuals never transmit the trait don t have the allele which would have been dominant and affected individuals always have at least one affected parent thus every generation o X linked recessive would only know which males are affected carrier circles are inferred from the pedigree analysis only way to know is if they re homozygous First clue that it s sex linked is that it s only showing up in males Affected male will never transmit to his sons because they get their X from mom but it does show up one generation later when the X allele that the father gave to the daughter gets passed to HER son Thus skipping generations classic recessive Once have the hypothesis start filling out the carrier circles in order to have the affected individuals that we do Unfortunately up to 10 of offspring have unexpected paternity across all human cultures which makes constructing the pedigree more difficult Famous case European royalty s hemophilia o X linked dominant Shows up in every generations Affected males pass the trait on to all of their daughters and none of their sons affected females pass it on to half of their daughters and half of their sons o Y linked traits appear only in males All male offspring of an affected male are affected No skipping generations To be Y linked father of affected children would always have to be affected Pedigree problems assume the disease is rare marrying in don t have assume that they re unrelated except for the relations shown in the pedigree will usually be a most likely answer but sometimes other modes of inheritance that can t be ruled out TEST what s the most likely mode of inheritance and what can you rule out o Many examples in the PowerPoint Putative Mendellian traits single Mendellian genes in human Earlobes tongue thumb on top pinky bending dry wet ear wax direction of hair whorl finger middle segment hair pigment double jointed teeth color finger length ratios for second and fourth fourth should be longer o Some are hormonally related like the finger lengths and not perfectly Mendellian Eugenics o Simple inheritance has been questioned after additional research and most traits involve multiple interacting genes with additional environmental influence o Nazis Law for the Prevention of Hereditarily Diseased Offspring requiring physicians to report hereditary illness except in women past childbearing age Most appeals were denied By the end of the war over 200 Hereditary Health courts and more than 400 000 people sterilized against their will In many countries including U S Denmark Norway Sweden Finland England etc o They were trying to weed out qualities like illiteracy or being poor or a drunk or an imbecile Dragging down society o Good book War against the weak by Edwin Black o The phenotypes they were studying were not Mendellian not to mention the ethical issues o 2 kinds of marriage prohibitions today biblical make no genetic sense like son in law with mother in law when they don t share genetics though there may be other good reasons not to mate and Western no close relatives first cousins in laws of any kind The Western prohibitions wary in what they consider close relatives o Common Indian custom is to marry first cousins big controversy in England right now because of load on health care system Ashkenazi Jews have high frequency of Tay Sachs disease most marriages are arranged so matchmakers implemented database to ensure that carrier of the allele are not paired preventing homozygotes Pre natal testing o Early detection of major chromosomal abnormalities assessing genotype in families with serious genetic disease and assessing biomarkers in the embryo indicative of developmental abnormalities o Easiest test maternal blood test Alpha fetoprotein neural tube defects ratio of hCG and PAPP A Down s o Other tests fetal tissue collection form fluid with ultrasound amniocentesis Chromosomal analysis Can also do Chorionic Villus Sampling CVS Chromosomal abnormalities o Different from 46 is an aneuploid o Aneuploidy usually results in prenatal death Having more or less chromosomes gives you about a thousand times more or less expression of genes imbalances o A few specific types are viable but have developmental syndromes o Usually are NOT inherited typically problem from mitosis o Frequency of chromosomal abnormalities increase with age women told that age 35 is a magic point on the curve not really Have oocytes that stopped in Meiosis I when we women were fetuses can get damaged before used or when Myosis starts again Probability rises rapidly when in 40 s o Frequency of aneuploidies 1 250 000 fertilizations 1 000 000 detected conceptions others chromosomal failures not detected 850 000 live births 150 000 miscarriages very early on mostly Huge table on PowerPoint of 100 000 pregnancies total 7500 chromosomal abnormalities in miscarriages 550 abnormalities in live births No miscarriages or live births for trisomy on Chromosome I huge