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 (becausesmall 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 aperfect 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 theallele, 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.o Simple inheritance has been questioned after additional research, and most traits involve multiple interacting genes with additional environmental influence.- Eugenicso 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 rightnow 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 MeiosisI 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) ->