1. congenital deformalities
2. cleft lip/palate
3. pyloric stenosis
4. clubbed foot
5. neural tube defects (prevented w/ 0.4 g of folic acid within first 4 wks of gestation)

• multifactorial inheritance
• single gene disorders
• multiple genes (microdeletions and microduplications)
• chromosomal abnormalities
• mitochondrial abnormalities

• 0.4 mg of folic acid per day
• if you have child with NTD already, 4 mg of folic acid per day

General gene density within each chromosome

Four principles of genetic counseling

• communication
• comprehension
• care
• confidentiality

• sexually reproducing organisms produce genes that occur in pairs
• only one member of this pair is transmitted to offspring (genes remain in tact and distinct)

KEY TO MODERN GENETICS!!!!!!!!!

• genes at different loci are transmitted independently
• a parent will transmit one allel from each locus to its offspring
• allele transmitted at one locus will have no affect on other locus

Ex: you can have a round with a wrinkled and you can have a tall with a short, and they will have no affect on each other if at different loci

Definition of multiplication rule

probability of two independent events occuring is the probability of event one times event two

probably that one event OR another will happen is added together (ex: probability of having a boy OR girl is 1)

If I have a patient who has a sibling with cystic fibrosis, given that it is 1/25 of all alleles in whites, what is the chance the brother is a carrier? Chance that he finds random white female and they have a baby with cystic fibrosis

• 2/3 (there is already one person who has the disease, so now its the other three Punnet squares to go to if both parents are carriers)
• 2/3 x 1/25 x 1/4

1/10 x 2/3 x 1/4 = 1/60

2/3 x 2/3 x 1/4 = 1/9

• estimate gene frequency from disease prevalence data
• estimate heterozygous carriers from recessive diseases

• if levels of phenylalanine accumulate in the blood and tissues, it can cause mental retardation due to brain dysfunction
• babies lose an average of 1-2 IQ pts for every week of life not treated

breast cancer

neurfibromatosis

Marfan's syndrome

familial hypercholesterolemia

polycystic kidney disease

breeding between first cousins or closer relatives

• new mutation
• germline mosaicism
• delayed age of onset
• reduced penetrance
• variable expression
• pleiotropy and heterogeneity
• genomic imprinting
• anticipation

What is implied in someone with a new mutation?

• gene transmitted by one of the parents that have not seen in previous generations
• change in DNA cause mutation from normal to disease bearing gene

What is the best way to determine that new mutations are the cause of a disease?

• occurs when you have a disease mutation that is not expressed
• elevates recurrence risk for future offspring of mosaic parent

a father could have a mutation, but his somatic cells are not effected, but offspring would be affected

• osteogenesis imperfecta
• achondroplasia
• duchennes muscular dystrophy
• hemophilia

• AD forms of breast cancer
• Hunington disease
• polycystic kidney disease
• hemochromatosis
• familial Alzheimer disease

It is very difficult to deduce the mode of inheritance, but you can find out later in life if an individual carries a mutation.

• individual who has genotype for disease may not exhibit disease pheonotype at all, even though he/she it can be transmittted to the next generation
• ex: retinoblastoma

• severity of disease can vary greatly
  • parent with mild expression of disease can tramsit gene to child who can have severe expression
    • (provide mechanism for disease genes to survive at higher frequencies in populations)

• environmental factors
• modifier genes
• allelic heterogeneity
  • ex: sicke cell, thalassemia

chromosome 16

• Africans have one deletion at each chromosome
• Asians have double deletion at one chromosome and have one normal chromosome

• genes that exert effects on multiple aspects of physiology/anatomy

• Marfan syndrome (AD condition in fibrillin located at chromosome 15q)
  • tall stature, long lengthy limbs, spider fingers, arched palate
  • affect eye, skeleton, CV system

Examples of pleiotropy

• cystic fibrosis
  • sweat glands, lungs, pancreas, genitourinary system
• osteogenesis imperfecta
  • bones, teeth, schlera
• sickle cell anemia
  • erythrocytes, bone, spleenb

Define locus heterogeneity

• caused by mutations in different loci in different loci in different families is said to exhibit locus heterogeneity 

Example of locus heterogeneity

• osteogenesis imperfecta
  • subunits of procollagen triple helix encoded by gwo genes
  • chromosome 17 and 7
  • mutation in either of these alters collagen structure leading to OI

• Prader-Willi
  • cause- deletion in 15q inherited from father
  • complication- short stature, obesity, mild/moderate mental retardation, hypogonadism
• Angelman syndrome
  • cause- deletion in 15q inherited from mother
  • complication- severe mental retardation, seizures, ataxic gate

genes inhertied from mother differ in some other way from those of the father, so the imprinting can alter activity of the genes, resulting in different phenotypes based on inheritance of mother and father

some genetic diseases seem to display earlier age of onset and/ormore severe expression in more recent generations

• Hunington's
• myotonic dystrophy
• fragile X syndrome
• spinocerebellar ataxia type I
• Machado-Joseph disease
• X link spinal and bulbar muscular atrophy
• fragile site FRAXE
• Friedreich's ataxia

cause of myotonic dystrophy

• cause- gene at chrom. 19 is expanded CTG trinucleotide repeat
  • number of repeats correlates with severity of disease

• Wilson's disease (recessive disorder)
• PKU

• siblings- 1/2 genes
• first cousins- 1/8 genes
• first cousins once removed- 1/16
• second cousins- 1/32