2. Animal and Human genetics & genetic disseases.pptx

Biology first year

1. Mammalian genetics and human genetic diseases

2. Sequencing Sanger sequencing Nanopore sequencing Sequencing by synthesis High throughput and fast Longer sections can be done More error prone Low throughput, slightly less error prone, good for small sections Impractical for whole genome High throughput and Fast Short sections assembled to whole genome in the computer Only slightly more error prone

3. Genomics Is the study of genomes, including large chromosomal segments containing many genes. The initial phase of genomics aims to map and sequence an initial set of entire genomes. Functional genomics aims to deduce information about the function of DNA sequences.

4. Bioinformatics to analyze genomes and their functions The Human Genome Project established databases and refined analytical software to make data available on the Internet Biological Data + Computer Calculations Bioinformatics

5. Three ways to access the human genome NCBI map viewer www.ncbi.nlm.nih.gov Ensembl Project (EBI/Sanger Institute) www.ensembl.org UCSC (Golden Path) www.genome.ucsc.edu And a very user friendly site focusing on gene variants causing disorders: https://omim.org/ Each of these three sites provides essential resources to study the human genome (and many other genomes) you can use them in the tutorial

6. QUESTION What do you notice about the size of the human genome and the number of genes om the next slide?

7.         The record-breaking species  Tmesipteris oblanceolata   is easy to miss on the forest floor.Credit : Pol Fernandez The record-breaking 160.45 Gbp species  Tmesipteris oblanceolata   is easy to miss on the forest floor.Credit : Pol Fernandez https://www.nature.com/articles/d41586-024-01567-7

8. Not strongly correlated to genome size The nematode C. elegans has 100 Mb and 20,100 genes, Drosophila has 165 Mb and 14,000 genes Predicted the human genome would contain about 50,000 to 100,000 genes; however the number is around 21,000 Eukaryote genomes can produce more than one polypeptide per gene because of alternative splicing of RNA transcripts Number of Genes

9. Content of the Human Genome Genes and associated sequences (~ 30 %) polypeptide-coding sequences (exons) (2%) non-coding sequences (introns) regulatory sequences Repetitive DNA (~50%) interspersed repeats: single, dispersed copies of sequences tandem repeats: adjacent repeats, also dispersed

10. Exon Intron Regulatory sequences The Human Genome: Gene Structure

11. Exons (1.5%) Regulatory sequences (5%) Introns ( ∼ 20%) Unique noncoding DNA (15%) Repetitive DNA that includes transposable elements and related sequences (44%) Repetitive DNA unrelated to transposable elements (14%) L1 sequences (17%) Alu elements (10%) Simple sequence DNA (3%) Large-segment duplications (5–6%)

12. Non-coding DNA Complex genomes have roughly 10x to 30x more DNA than is required to encode all the RNAs or proteins in the organism. Contributors to the non-coding DNA include: Introns in genes Regulatory elements of genes Multiple copies of genes, including pseudogenes Intergenic sequences Interspersed repeats

13. Noncoding DNA found between genes Pseudogenes are former genes that have accumulated mutations and are nonfunctional Repetitive DNA is present in multiple copies in the genome About three-fourths of repetitive DNA is made up of transposable elements and sequences related to them Intergenic DNA

14. Repetitive DNA About 15% of the human genome consists of duplication of long sequences of DNA from one location to another A series of repeating units of 2 to 5 nucleotides is called a short tandem repeat (STR) The repeat number for STRs can vary among sites (within a genome) or individuals Simple sequence DNA is common in centromeres and telomeres, where it probably plays structural roles in the chromosome

15. STRs are variations in the number of repeats of specific DNA sequences PCR and gel electrophoresis are used to amplify and then identify STRs of different lengths The probability that two people who are not identical twins have the same STR markers is exceptionally small DNA Profiling

16. Earl Washington just before his release in 2001, after 17 years in prison. These and other STR data (not shown) exonerated Washington and led Tinsley to plead guilty to the murder. Source of sample STR marker 1 STR marker 2 STR marker 3 Semen on victim 17,19 13,16 12,12 Earl Washington 16,18 14,15 11,12 Kenneth Tinsley 17,19 13,16 12,12

17. Transposon New copy of transposon DNA of genome Transposon is copied Insertion Mobile copy of transposon Transposon

18. Retrotransposon New copy of retrotransposon Insertion Mobile copy of retrotransposon Synthesis of a single-stranded RNA intermediate RNA Reverse transcriptase DNA strand Retrotransposon

19. Sequences Related to Transposable Elements Multiple copies of transposable elements and related sequences are scattered throughout eukaryotic genomes In primates, a large portion of transposable element–related DNA consists of a family of similar sequences called Alu elements Many Alu elements are transcribed into RNA molecules; some are thought to help regulate gene expression Article Source: Three-Dimensional Maps of All Chromosomes in Human Male Fibroblast Nuclei and Prometaphase Rosettes Bolzer A, Kreth G, Solovei I, Koehler D, Saracoglu K, et al. (2005) Three-Dimensional Maps of All Chromosomes in Human Male Fibroblast Nuclei and Prometaphase Rosettes. PLOS Biology 3(5): e157. https://doi.org/10.1371/journal.pbio.0030157

20. To understand evolution and genetic disease we need to understand how new genetic information is generated and how genetic diversity is maintained

21. We talked about: Insertional elements Meiosis and sex Today: Mutations

22. MUTATIONS Changes in DNA that affect genetic information

23. A natural or human-made agent (physical or chemical) which can alter the structure or sequence of DNA. Chemical mutagens base analogs ( bromouracil ) Chemicals which alter structure and pairing of bases (nitrous acid) Intercalating agents (ethidium bromide) DNA structure altering (peroxides) Radiation EM spectrum Ionizing radiation Mutagens

24. Mutations in the Genome A genome mutation may be limited to a single base, or may affect a large segment of a chromosome Mutations in somatic (body) cells cannot be passed on to the offspring, but can give rise to diseases such as cancer Germ-line mutations (mutations in gamete-producing cells) can be passed on to the offspring

25. Mutation Diploid germ-line cell Haploid gamete cells The process of Meiosis is shown in this slide

26. Mutation Diploid germ-line cell Haploid gamete cells The process of Meiosis is shown in this slide

27. Gene Mutations A gene mutation is one that affects only a single gene Point mutations a base change in the DNA can be silent, missense or nonsense Insertion and deletion mutations addition or removal of one or more nucleotides may introduce frameshift mutations

28. The genetic code – Recap DNA (template strand) messengerRNA Polypeptide Normal gene 3’TACGGTCTCCTCACG5’ ↓ 5’AUGCCAGAGGAGUGC3’ Codons ↓ Met-Pro-Glu-Glu- Cys Amino acids The antisense strand is the DNA strand which acts as the template for mRNA transcription

29. Coding strand 5 ′ -ATA TTA GCT GAC-3 ′ Template strand 3 ′ -TAT AAT CGA CTG-5 ′ Messenger RNA 5 ′ -AUA UUA GCU GAC-3 ′ Polypeptide Ile Leu Ala Asp Coding strand 5 ′ -ATA TTA GCC GAC-3 ′ Template strand 3 ′ -TAT AAT CGG CTG-5 ′ Messenger RNA 5 ′ -AUA UUA GCC GAC-3 ′ Polypeptide Ile Leu Ala Asp Mutation Silent mutation

30. Coding strand 5 ′ -ATA TTA GTC GAC-3 ′ Template strand 3 ′ -TAT AAT CAG CTG-5 ′ Messenger RNA 5 ′ -AUA UUA GUC GAC-3 ′ Polypeptide Ile Leu Val Asp Coding strand 5 ′ -ATA TTA GCC GAC-3 ′ Template strand 3 ′ -TAT AAT CGG CTG-5 ′ Messenger RNA 5 ′ -AUA UUA GCC GAC-3 ′ Polypeptide Ile Leu Ala Asp Mutation Missense mutation

31. Coding strand 5 ′ -ATA TAA GCC GAC-3 ′ Template strand 3 ′ -TAT ATT CGG CTG-5 ′ Messenger RNA 5 ′ -AUA UAA GCC GAC-3 ′ Polypeptide Ile Coding strand 5 ′ -ATA TTA GCC GAC-3 ′ Template strand 3 ′ -TAT AAT CGG CTG-5 ′ Messenger RNA 5 ′ -AUA UUA GCC GAC-3 ′ Polypeptide Ile Leu Ala Asp Mutation Nonsense mutation

32. Coding strand 5 ′ -ATA TTA TGC CGA C-3 ′ Template strand 3 ′ -TAT AAT ACG GCT G-5 ′ Messenger RNA 5 ′ -AUA UUA UGC CGA C-3 ′ Polypeptide Ile Leu Cys Arg Coding strand 5 ′ -ATA TTA GCC GAC-3 ′ Template strand 3 ′ -TAT AAT CGG CTG-5 ′ Messenger RNA 5 ′ -AUA UUA GCC GAC-3 ′ Polypeptide Ile Leu Ala Asp Mutation Insertion mutation

33. Coding strand 5 ′ -ATA TTA GCC GAC-3 ′ Template strand 3 ′ -TAT AAT CGG CTG-5 ′ Messenger RNA 5 ′ -AUA UUA GCC GAC-3 ′ Polypeptide Ile Leu Ala Asp Coding strand 5 ′ -ATA TTA CCG AC -3 ′ Template strand 3 ′ -TAT AAT GGC TG -5 ′ Messenger RNA 5 ′ -AUA UUA CCG AC -3 ′ Polypeptide Ile Leu Pro Thr Mutation Deletion mutation

34. Nomenclature for mutations Format : "reference : description" (e.g., NM_004006.2:c.4375C>T, NC_000023.11:g.32389644G>A) DNA Level : coding DNA sequence(c.) or genomic sequence" (g.). RNA/Protein Level : (r. for RNA, p. for protein). Reference Sequences Format : NC_000023.10 (NC_000023 is the accession number, .10 is the version number). Genome Builds : Common builds include hg18/NCBI36, hg19/GRCh37, Chromosome Location Chromosome Number : Indicates the chromosome (e.g., 23 for X chromosome). Cytogenetic Bands : Locations given as loci on cytogenetic bands (e.g., Xq28). Example Descriptions Genomic (Nucleotide) : NC_000023.11:g.32389644G>A Transcript (RNA) : NM_004006.2:c.4375C>T Protein (Amino Acid) : NP_003997.1:p.Arg1459Ter Types of Variants Substitution : c.4375C>T (C to T) Deletion : c.4375_4379del (CGATT deleted) Duplication : c.4375_4385dup (CGATTATTCCA duplicated) Insertion : c.4375_4376insACCT (ACCT inserted) Deletion/Insertion : c.4375_4376delinsAGTT (CG deleted, AGTT inserted)

35. An  allele  is a variant form of a gene. Some genes have a variety of different forms, which are located at the same position, or genetic locus, on a chromosome. Humans are called diploid organisms because they have two alleles  at each genetic locus in their somatic cells with one  allele inherited from each parent. The gametes a haploid. So they have only one allele Alleles

36. A  recessive  allele only shows if the individual has two copies of it. For example, the allele for blue eyes is recessive. You need two copies of this allele to have blue eyes. A  dominant  allele always shows, even if the individual only has one copy of it. For example, the allele for brown eyes is dominant. You only need one copy of it to have brown eyes. Two copies will still give you brown eyes. Alleles may be recessive or dominant

37. Parents A parent who is a carrier of an autosomal recessive allele has one copy of a normal gene and one copy of an altered gene of the particular pair AUTOSOMAL RECESSIVE INHERITANCE

38. Parents Gametes A carrier parent passes on either the normal gene or the altered gene into the eggs or sperm The other carrier parent passes on either the normal gene or the altered gene into his/her eggs or sperm AUTOSOMAL RECESSIVE INHERITANCE

39. Parents Gametes There are four different combinations of the two genes from each parent AUTOSOMAL RECESSIVE INHERITANCE

40. Parents Gametes Offspring AUTOSOMAL RECESSIVE INHERITANCE

41. Parents Gametes Offspring AUTOSOMAL RECESSIVE INHERITANCE

42. Parents Gametes Offspring AUTOSOMAL RECESSIVE INHERITANCE

43. Parents Gametes Offspring Which children are affected by the disease? AUTOSOMAL RECESSIVE INHERITANCE

44. Parents Gametes Affected Unaffected Unaffected Unaffected AUTOSOMAL RECESSIVE INHERITANCE

45. At conception, Each child of two parents who are carriers for the same autosomal recessive disorder therefore has a 1/4 (25%) chance of neither being affected nor a carrier of the disease 1/2 (50%) chance of being a carrier but unaffected 1/4 (25%) chance of inheriting the disease Summary

46. More complex inheritance

47. More complex inheritance

48. More complex inheritance

49. More complex inheritance Quantitative characters vary continuously in a population. This variation often shows polygenic inheritance, where multiple genes add up to affect one trait. Human skin colour is an example of this.

50. More complex inheritance Epistasis  is when one gene changes how another gene shows up. In mice and many mammals, coat colour depends on two genes: One gene decides the pigment colour (B for black, b for brown). Another gene (C for colour, c for no colour) decides if the pigment goes into the hair. So, even if a mouse has black or brown pigment genes, the “c” allele (no colour) can stop the pigment from being in the hair, changing the coat colour.

51. Nurture vs Nature or Nurture & Nature Not everything is genetic Phenotypes are formed in an interplay between physiology, environment and genotype

52. Diversity of life Diverse figures from Wikipedia/ Wikimedia or Bart Pander

53. Evolutionary mechanisms From the genetic perspective Evolution is the change over time in gene variant frequencies in the population.

54. Evolutionary mechanisms Population growth & Reproduction : Organisms reproduce, often producing more offspring than the parents, which would lead to an exponential population growth. However: Resource Limitation : As the population grows, space and resources inherently become limited which leads to competition. Variation : Offspring are not identical to their parents due to mutations and sexual reproduction, resulting in variation within the population. Natural Selection : Due to this variation, some individuals are better adapted to their (limited) environment and thus more successful at reproducing. These individuals pass on their advantageous traits to their offspring. Genetic Drift : But even without natural selection random changes in allele frequencies can also influence the genetic makeup of a population, especially in small populations. Speciation : Over time, slow evolutionary changes combined with reproductive isolation can lead to the formation of new species.

55. Evolutionary mechanisms From the genetic perspective Evolution is the change of gene variant frequencies in the population. Hardy & Weinberg had the realisation that Mendelian genetics imply gene frequencies remaining stabile in a population if: Absolutely no mutations Completely random mating No natural selection Extremely large (nearly infinite) population No gene flow This never is true in nature! Therefore there is always some evolution, sometimes very little, sometimes a lot ! If population is in H-W equilibrium i.e. their 5 points are met: p 2 + 2pq + q 2 =1 where p and q are the frequencies of the alleles p 2 are and q 2 the frequencies of homozygotes 2pq the frequency of the heterozygotes

56. Evolutionary mechanisms Absolutely no mutations Completely random mating No natural selection Extremely large (nearly infinite) population No gene flow If population is in H-W equilibrium i.e. their 5 points are met: p 2 + 2pq + q 2 =1 where p and q are the frequencies of the alleles p 2 are and q 2 the frequencies of homozygotes 2pq the frequency of the heterozygotes

57. Gene Disorders Most inherited gene disorders in humans are autosomal recessive There may be multiple recessive alleles of ‘ disease ’ genes Some inherited gene disorders are sex-linked caused by a recessive allele on the X chromosome normally only expressed in males There are also some dominant disorders . More about them later.

58. Autosomal recessive disorder : Sickle Cell Anemia Normal Red Blood Cell Red blood cells shaped like a rounded disc Hemoglobin (protein) carries oxygen to all parts of the body Sickle Red Blood Cell Red blood cells form an abnormal crescent shape Hemoglobin (protein) can become abnormally shaped under low pO2 don't move easily through your blood vessels form clumps and get stuck in the blood vessels a missense mutation which causes a single amino acid in β globin to change from glutamate to valine HBB Gene: T>A,C,G Position chr11:5227002 (GRCh38.p14) (short arm of chromosome 11 band 14) SPDI:NC_000011.10:5227001:T:A,NC_000011.10:5227001:T:C,NC_000011.10:5227001:T:G

59. Population genetics, evolution and disease prevalence Genetic disease and population genetics         Figure 3.27  In this blood smear, visualized at 535x magnification using bright field microscopy, sickle cells are crescent shaped, while normal cells are disc-shaped. (credit: modification of work by Ed Uthman; scale-bar data from Matt Russell)

60. Population genetics, evolution and disease prevalence p 2 + 2pq + q 2 =1 If q= sickle cell allele frequency and p=normal HBB q =0.125(12.5%) p =0.875 (87.5%) p 2 = 0.76 homozygous normal HBB (susceptible to malaria) 2pq = 0.22 Heterozygous (less susceptible to malaria, no other issues) q 2 = 0.02 homozygous scHBB (less susceptible to malaria, but suffering from Sickle cell anaemia which is arguably just as bad, or worse)

61. Phenylketonuria or PKU PKU is a autosomal recessive disorder Caused by a deficiency of an enzyme which is necessary for proper metabolism of an amino acid called phenylalanine. Enzyme defective is called phenylalanine hydroxylase (PAH) The coding gene is on chromosome 12(   12:102,836,889-102,958,441 ) Phenylalanine is an essential amino acid and is found in nearly all foods which contain protein, dairy products, nuts, beans, tofu… etc. Symptoms : Loss of the PAH enzyme results in intellectual disability, organ damage, unusual posture and can, in cases of maternal PKU, severely compromise pregnancy.

62. Mutations in both copies of the gene for PAH means that the enzyme is inactive or is less efficient, and the concentration of phenylalanine and phenylpyruvate in the body can build up to toxic levels. Biochemical basis of PKU

63. Phenylketonuria In the UK and many other countries, newborn children are screened for PKU using a simple blood test controlled by a diet low in phenylalanine (and high in tyrosine).

64. People often ask the question Why are there high levels of PKU in the population

65. Does evolution explain the high incidence of PKU in humans? A deleterious mutation should be eliminated from the gene pool, but the deadly PKU allele has instead survived and spread widely…..WHY? Carriers of PKU ( +/ pku heterozygotes) have elevated phenylalanine levels Women who are PKU carriers have a lower-than-average incidence of miscarriage Rationale : If PKU carriers were more likely to have children than non-carriers because of the protective effects of the PKU gene, then over time, the disease-causing allele would increase and spread through the population.

66. Progeny +/+ +/ pku +/ pku pku / pku X ¼ ½ ¼ Parents +/ pku x +/ pku 50% pku frequency Much more susceptible to miscarriage reducing reproductive success Genes are selected for their reproductive fitness, even if the consequences for some individuals is disastrous These individuals die early The 50% is for the example, it is. More like ~1% in European populations

67. Example: Cystic Fibrosis (CF) What is it? Autosomal, recessive disorder Symptoms Thick mucus in the lungs and digestive track Constant lung infections and impaired digestion

68. Cystic fibrosis Broken salt channel in cells strikes 1 in 2500 births in UK gene codes for a protein channel that allows salt to flow across cell membrane broken protein doesn’t work as channel doesn’t allow salt out of cell, so water doesn’t flow out either thicker & stickier mucus coating around cells mucus build-ups in lungs & causes bacterial infections destroys lung function without treatment children die before 5; with treatment can live past their late 20s

69. deletion Loss of one amino acid ! Cause of Cystic Fibrosis (CF) Mutant protein is missing an amino acid and cannot fold correctly vs

70. Effect on Lungs Salt channel transports salt through protein channel out of cell Osmosis problems ! airway salt H 2 O H 2 O salt normal lungs cystic fibrosis cells lining lungs salt channel normal mucus thick mucus mucus & bacteria build up = lung infections & damage 

71. Heterozygous advantage? Maybe protection against severe diarrhoea, especially against Cholera? 1 in 25 of the population is carrier of a CF gene in certain parts of the world!

72. Huntington’s Disease An autosomal dominant disorder Huntington's disease (HD) is an inherited, degenerative brain disorder which results in an eventual loss of both mental and physical control. The disease is also known as Huntington's chorea. Chorea means "dance-like movements" and refers to the uncontrolled motions often associated with the disease.

73. Huntington’s Disease Caused by mutation of the Huntington gene ( HTT ) The gene is also called HD and IT15 , which stands for “interesting transcript 15” The gene has a repeated section called a trinucleotide repeat , which varies in length between individuals and may change length between generations When the length of this repeated section reaches a certain threshold, it produces an altered from of the protein called mutant Huntington protein ( mHTT ) This newly altered protein form, increases the decay rate of certain types of neurons

74. Huntington’s Disease

75. Alleles for Dominant disorders are rarer than recessive: why? Selection against is more direct. Dominant disorders are often not very serious, or only until after the reproductive age; why? No (or very little) selection pressure against a disorder that allows normal reproduction. Dominant disorders that do have considerable negative effects before the age of reproduction are selected against and extremely unlikely to be inherited, but can be caused by dominant de novo mutations!

76. Hemophilia A g enetic disorder that prevents the blood from clotting properly, resulting in excessive bleeding A sex-linked recessive trait, primarily carried by males (found on the x chromosome)

77. Sex-linked disorders X-linked recessive disorders are much more prevalent in men; why? Because if they inherit the recessive allele carrying X they will not have a dominant allele to compensate. Colour blindness is one of the most common X-linked disorders affecting about 8% of males . The Y chromosome is inherited patrilineal only but Y-linked genetic disorders are rare even in male, why? Because the Y chromosome is tiny and caries almost no genes . And/ or the x-chromosomal genes can compensate. The mitochondrial genomes are only inherited in the maternal line, i.e we inherited them all from our moms. The genome is small though the few genes are very important! Mitochondrial genomic diseases are often de novo mutations. x Y Mt

78. Complex Disorders Many diseases are inheritable but in a complex fashion. Complex disorders (e.g., cardiovascular disease) are subject to a large variety of many genetic and environmental effects. Some complex disorders are quantitative traits display continuous variation influenced by alleles of several or many different genes Mutated alleles often have more than one effect on the phenotype (pleiotropy)

79. Chromosome Disorders Change in chromosome structure inherited disorders in chromosome structure are rare common in cancer cells Changes in chromosome number best known is an extra copy of chromosome 21 (Down syndrome) changes in the number of sex chromosomes can also occur Most Chromosome disorders are not viable and cause a large proportion of early pregnancy miscarriages! The ones we know more about are those that are viable (although still lead to disorders)

80. Chromosomal Mutations Any change in the structure or number of chromosomes Large scale: Affect many genes

81. Chromosome Mutations Inversion : a segment of a chromosome is inverted Deletion : a segment of a chromosome is deleted Translocation : segments of different chromosomes are exchanged Duplication : a segment of one chromosome moves to the same location on a homologous chromosome

82. Chromosomal Deletion One or more genes are removed Causes: Wolf-Hirschhorn syndrome (severe intellectual disability ) cri du chat syndrome (mewing sounds, intellectual disability )

83. cri du chat syndrome Caused by a deletion of part of chromosome 5. Most cases occur spontaneously through the germ-line. The term cri du chat ('cry of the cat') refers to the characteristic meow-like cry of affected infants. Mental and physical development in affected individuals is impaired.

84. Chromosomal Duplication A segment of genes is copied twice and added to the chromosome Causes: Charcot–Marie–Tooth disease (high arched foot, claw feet, confined to a wheelchair)

85. Chromosomal Inversion a segment of genes flip end-to-end on the chromosome Causes: Four-Ring Syndrome (cleft pallate , club feet, testes don’t descend)

86. Chromosomal Translocation Material is swapped with another chromosome Causes: Burkitt’s Lymphoma (cancer of the lymph nodes, in children)

87. Nondisjunction Chromosomes FAIL TO SEPARATE during meiosis Produces gametes (and therefore a baby) with one missing chromosome or one extra chromosome

88. Changes in Chromosome Number Caused by nondisjunction (failure to separate) of chromosomes or chromatids during meiosis Gametes may then contain an abnormal number of chromosomes ( aneuploidy ) Gain of a chromosome in a zygote is sometimes tolerated; loss of an autosome is always lethal As many as 5% of human zygotes may be aneuploid, but most do not survive the first trimester

89. Meiosis I Meiosis II The correct separation of a pair of homologous chromosomes and their chromatids during meiosis

90. Meiosis I Meiosis II aneuploidy

91. Meiosis I Meiosis II

92. Down’s Syndrome Caused by non-disjunction of the 21 st chromosome. This means that the individual has a trisomy (3 – 2lst chromosomes). 1 3 2 5 4 7 6 8 10 9 11 12 13 15 14 19 16 17 18 21 20 X 22 Y

93. Klinefelter’s syndrome Disorder occurring due to nondisjunction of the X chromosome. The Sperm containing both X and Y combines with an egg containing the X, results in a male child . The egg may contribute the extra X chromosome.

94. Symptoms of Klinefelter’s

95. Turner syndrome Chromosomal or monogenic? Associated with underdeveloped ovaries, short stature, webbed, and is only in women. Bull neck, and broad chest. Individuals are sterile, and lack expected secondary sexual characteristics.

96. Genetic Medicine? Gene therapy using an adenovirus vector can be used to cure certain genetic diseases in which a person has a defective gene. This was highly experimental with high failure rate for many years but in the last 4 years there have been many improvements in the field (credit: NIH)