BICOL UNIVERSITY

Legazpi City
Graduate School
Date:09-09-2020
Name of Student: ROMEL B. BAYABAN
Course: MABioEd-211 (Advanced Genetics)
Professor: MA. EDEN A. ANTE_____________

PERFORMANCE TASKS

A. FEATURED ARTICLE
Read the featured article on page 9 of your pdf copy on page 44 entitled Modern Approaches to
Understanding Gene Function: Identifying Mendel’s gene for regulating white flower color in peas. You
can also read the original article by Hellens, RP et.al written as reference to the material. Then answer
the two questions in the Questions to consider portion found at the rightmost bottom of the page.
(20 points )

1. Why do you think that expression of gene A appears as spots in the leaves/petals shown in the
photo on the left? What does this signify?

Answer: To confirm gene A function, researchers delivered normal copies of gene A into white
flower petals by using a gene gun, a device that shoots metal particles coated with a gene of interest
into cells. In this approach, gold particles coated with gene A enter a small percentage of cells and
gene A is expressed into those cells. Forty-eight hours after particle bombardment, numerous purple
colored cells were seen that appeared as spots. This signifies or manifests the accumulation of
anthocyanin pigment and turn purple. The inset square shows a higher magnification image
enlarging spots of gene A expression in the petals.

2. If you did the same experiment with a pea plant that had a mutation in the gene for anthocyanin
accumulation, would you expect that introduction of gene A would rescue the phenotype of the
mutant? Why or why not?

Answer: If I did the same experiment with a pea plant that had a mutation in the gene for
anthocyanin, I expect that the introduction of gene A will rescue the phenotype of the mutant. As
we know, gene A encodes a transcription factor, a protein which controls anthocyanin synthesis and
hence produces purple flowers. This is an example of what geneticists call a rescue experiment
because in cells that receive gene A the white flower mutant phenotype was rescued or restored to
the purple, wild type phenotype. It happens when the gene A encodes a transcription factor that
binds to DNA and regulates expression of other genes. When this transcription factor was able to
switch on the expression of genes involved in making anthocyanin pigments in pea flowers and were
able to make them purple, we can say that it is effective in rescuing the phenotype of the mutant.
B. PRACTICE PROBLEMS
Solve the problems (highlighted in yellow ) in your pdf (page 41, problem 3.1; page 45, problem
3.2; page 46, problem 3.3; page 52, problem 3.4; and page 54, problem 3.5. )Show your solution and
explanation for each. (25 points )

Now Solve this 3.1-Page 41

In order to solve for the possible crosses appropriate in each problem, we need to set this up in the
table and look for the ratios and trends. (I made the illustration in the power point and pasted it here.)

P1 Crosses F1 Progeny Ratio of Appropriate Progeny

Checkere Plain Checkered Possible Checkere Plain
d to plain Crosses d
a. checkered x 36 0 1:0 PP x PP PP
checkered
b. checkered x plain 38 0 1:0 PP x pp Pp
c. plain x plain 0 35 0:1 pp x pp pp
F2 Progeny
F1 x F1 Crosses
d. checkered (a) x plain 34 0 1:0 PP x pp Pp
(c)
 e. checkered (b) x plain 17 14 1:1 Pp x pp Pp pp
(c)
f. checkered (b) x 28 9 3:1 Pp x Pp PP, Pp pp
checkered (c)
g. checkered (a) x 39 0 1:0 PP x Pp PP, Pp
checkered (b)

Let P represents for Checkered and p for Plain since according to the convention, the first letter of the
recessive trait symbolizes the character in question.

Solutions A. CHECKERED X CHECKERED Solutions B. CHECKERED X PLAIN

F2 Generation F2 Generation
P P P P
P PP PP p Pp Pp
P PP PP p Pp Pp
F2 Results F2 Results

Genotypic Ratio Phenotypic Ratio Genotypic Ratio Phenotypic Ratio

4 PP 4/4 Checkered 4 Pp 4/4 Checkered

4:0 4:0 4:0 4:0

As seen in the illustration above, the factors occur in
pairs. These paired unit factors separate or segregate
randomly so that each gamete receives one or the other
with equal likelihood. A cross between two homozygous
dominant parents in the case for checkered pigeons
resulted to all checkered progenies.
As seen in the illustration above, a cross between a
homozygous dominant alleles and homozygous recessive
alleles resulted to all heterozygous traits which of still a
dominant trait based on mendelian genetics. When
dominant checkered pigeons are crossed with recessive
plain pigeons, it resulted to all checkered progenies.
Solutions C. PLAIN X PLAIN

F2 Generation P P As seen in the illustration above, a cross

P PP PP between two homozygous recessive alleles
P PP PP resulted to all homozygous recessive traits. In
F2 Results the case of color pattern for pigeons, when plain
Genotypic Ratio Phenotypic Ratio colored pigeons were mated with another plain
4 pp 4/4 plain colored pigeons, it resulted to all plain colored
traits for the progenies. In this problem, no
4:0 4:0
dominant traits were present to suppressed the
recessive allele.
Solutions D. CHECKERED X PLAIN

F2 Generation P P All checkered progenies in the F2

p Pp Pp generation
p Pp Pp

F2 Results Genotypic Ratio Phenotypic Ratio

4 Pp 4/4 Checkered

4:0 4:0

As seen in the illustration above, a cross between a homozygous dominant

alleles and homozygous recessive alleles resulted to all heterozygous traits
which of still a dominant trait based on mendelian genetics. When dominant
checkered pigeons are crossed with recessive plain pigeons, it resulted to all
checkered progenies.
Solutions E. CHECKERED X PLAIN

P p 2 checkered and 2 plain

F2 Generation p Pp pp progenies
p Pp pp

Genotypic Ratio Phenotypic Ratio

F2 Results 2 Pp 2/4 Checkered

2 pp 2/4 plain

2:2 2:2

As seen in the illustration above, a cross between a heterozygous dominant alleles Pp

and homozygous recessive pp alleles resulted to 50-50 ratios of progenies. It resulted
to 50% of checkered and 50% of plain progenies. For as long as one of the parents have
a dominant allele even if it is crossed with a homozygous recessive alleles, it will always
show a dominant trait in the progenies. If both parents carry the homozygous recessive
alleles, they will not have a progeny with a dominant trait.
Solutions F. CHECKERED X PLAIN

F2 Generation P p 3 checkered and 1 plain

P PP Pp progenies
p Pp pp
Genotypic Ratio Phenotypic Ratio
F2 Results 1 PP

2 Pp 3/4 Checkered

1 pp 1/4 plain

1:2:1 3:1

As seen in the illustration above, a cross between two heterozygous dominant alleles
Pp alleles resulted to 3:1 ratios of dominant traits over the recessive traits in the
progenies. It resulted to 75% checkered and 25% plain colored traits in the progenies.
Solutions F. CHECKERED X CHECKERED

P P All checkered
F2 Generation
P PP PP
p Pp Pp

Genotypic Ratio Phenotypic Ratio

F2 Results
2 PP

2 Pp 4/4 Checkered

2:2 4:0

As seen in the illustration above, a cross between a homozygous dominant alleles PP

alleles with heterozygous dominant alleles Pp resulted to all checkered colored
progenies.
Now Solve this 3.2-Page 45

Considering the Mendelian traits round versus wrinkles and yellow versus green, consider the
crosses below and determine the genotypes of the parental plants by analyzing the phenotypes of their
offspring.

a. round, yellow x round, yellow

Required Result for
Offspring:

3/4 round, yellow

1/4 wrinkled, yellow

F2 Genotypic ratio F2 Phenotypic ratio

WWGG : 4/16 Round, yellow

WwGG : 8/16 Round, yellow 12/16 or 3/4
wwGG : 4/16 Wrinkled, yellow : 4/16 or 1/4
GR: 4:8:4 or 1:2:1 PR: 12:4 or 3:1
b. wrinkled, yellow x round, yellow
Required Result for
Offspring:

6/16 wrinkled, yellow

2/16 wrinkled, green

6/16 round, yellow

2/16 round, green

F2 Genotypic ratio F2 Phenotypic ratio

WwGG : 2/16 Round, yellow

WwGg : 4/16 Round, yellow 6/16
Wwgg : 2/16 Round, green : 2/16
wwGG : 2/16 Wrinkled, yellow
wwGg : 4/16 Wrinkled, yellow 6/16
wwgg : 2/16 Wrinkled, green : 2/16
c. round, yellow x round, yellow
Required Result for
Offspring:

9/16 round, yellow

3/16 round, green

3/16 wrinkled, yellow

1/16 wrinkled, green

F2 Genotypic ratio F2 Phenotypic ratio

WWGG : 1/16 Round, yellow

WWGg : 2/16 Round, yellow
WwGG : 2/16 Round, yellow Round, yellow : 9/16
WwGg : 4/16 Round, yellow
WWgg : 1/16 Round, green
Wwgg : 2/16 Round, green Round, green : 3/16
wwGG : 1/16 Wrinkled, yellow
wwGg : 2/16 Wrinkled, yellow Wrinkled, yellow : 3/16
wwgg : 1/16 Wrinkled, green Wrinkled, green : 1/16
GR: 1:2:2:4:1:2:1:2:1 PR: 9:3:3:1
d. round, yellow x wrinkled, green
Required Result for
Offspring:

1/4 round, yellow

1/4 round, green

1/4 wrinkled, yellow

1/4 wrinkled, green

F2 Genotypic ratio F2 Phenotypic ratio

WwGg : 4/16 Round, yellow : 4/16 or 1/4

Wwgg : 4/16 Round, green : 4/16 or 1/4
wwGg : 4/16 Wrinkled, yellow : 4/16 or 1/4
wwgg : 4/16 Wrinkled, green : 4/16 or 1/4
GR: 4:4:4:4 or 1:1:1:1 PR: 4:4:4:4 or 1:1:1:1

Now Solve This 3.3-Page 46

Using the forked-line, or branch diagram method, determine the genotypic and phenotypic
ratios of these trihybrid crosses: ( I made the illustration and solving in power point, then converted and
pasted it here in word)

(a) AaBbCc x AaBBCC

(b) AaBBCc x aaBBCc
(c) AaBbCc x AaBbCc

Steps:

1. Predict the outcomes of each cross for the A/a, B/b and C/c genes through a punnet square or
test cross.
2. Get the ratio of the progeny for each trait then do the fork-line/branch diagram method.
PR: 1:2:1:2:4:2:1:2:1:2:4:2:4:8:4:2:4:2:1:2:1:2:4:2:1:2:1
Now Solve This 3.4-Page 52

In one of Mendel’s dihybrid crosses, he observed 315 round, yellow; 108 round, green; 101
wrinkled, yellow; and 32 wrinkled, green F 2 plants. Analyze these data using the x2 test to see if

(a) They fit a 9:3:3:1 ratio

(b) The round: wrinkled data fit a 3:1 ratio
(c) The yellow: green data fit a 3:1 ratio

Ho : There is no significance difference between observed data and the predicted data.
a. They fit a 9:3:3:1 ratio

Dihybrid
Phenotype Cross Observed Expected (e) Deviation Deviation2 d2/e
Expected (o) (o-e=d)
Ratio
Round,yellow 9/16 315 9/16(556)=312.75 2.25 5.0625 0.0162
Round,green 3/16 108 3/16(556)=104.25 3.76 14.1376 0.1356
Wrinkled,yello 3/16 101 3/16(556)=104.25 -3.25 10.5625 0.1013
w
Wrinkled,green 1/16 32 1/16(556)=34.75 -2.75 7.5625 0.2176
556 x2
=0.4707
Degrees of freedom (df) = 3 Probability value (p) = .9253

The goal here is to determine if the observed data fit the given expected ratios. Chi-square
formula will be use to test the null hypothesis. The null hypothesis (Ho) states any deviation from the
expected value is due to chance. If the null hypothesis(Ho) fails to be rejected, then the observations fit
the ratio. If the null hypothesis(Ho) is rejected, then the observations do not fit the expected ratio.

For this problem, the x2 statistics is 0.4707 while the degrees of freedom is 3.

P (x2 >0.4707)=.9253

In here, we fail to reject Ho , as p =.9254 > α= .05. Since there is no significant difference
between the observed data and predicted data.

Based from the result, it was observed that:

(a) they fit a 9:3:3:1 ratio where p =.9254 > α= .05

Therefore, null hypothesis is accepted.

Note: To compute for the probability values, I used the Chi-Square calculator online in this link.

https://www.socscistatistics.com/pvalues/chidistribution.aspx
b.The round: wrinkled data fit a 3:1 ratio

Phenotype Cross Observed (o) Expected (e) Deviation Deviation2 d2/e

Expected (o-e=d)
Ratio
Round 3/4 (315+108)=423 3/4(556)=417 6 36 0.086
Wrinkled 1/4 (101+32)= 133 1/4(556)=139 -6 36 0.259
556 x2
=0.345
Degrees of freedom (df) = 1 Probability value (p) = .55

The result is not significant at p <.05

To check the 3:1 fit ratio, compute for the proportion of total

Seed Shape Round Wrinkled

No. of plants 315+10= 423 101+32=133
Proportion of total 76% or ¾ ( 3) 24% or ¼ (1)
Based from the result, it was observed that:

(b) The round: wrinkled data fit a 3:1 ratio where p =.55 > α= .05

c. The yellow: green data fit a 3:1 ratio

Phenotype Cross Observed (o) Expected (e) Deviation Deviation2 d2/e

Expected (o-e=d)
Ratio
Yellow 3/4 (315+101)=416 3/4(556)=417 1 1 0.0024
Green 1/4 (108+32)= 140 1/4(556)=139 1 1 0.0072
556 x2
=0.0096
Degrees of freedom (df) = 1 Probability value (p) = .92

The result is not significant at p <.05

To check the 3:1 fit ratio, compute for the proportion of total

Pea Color Yellow Green

No. of plants 315+101= 416 108+32=140
Proportion of total 75% or ¾ ( 3) 25% or ¼ (1)
Based from the result, it was observed that:

(c) The yellow: green data fit a 3:1 ratio where p =.92 > α= .05
Now Solve This 3.5-Page 54
The following pedigree is for myopia (nearsightedness) in humans.

Predict whether the disorder is inherited as the result of a dominant or recessive trait.
Determine the most probable genotype for each individual based on your prediction.

I
II

Probable genotypes
III
here are either NN
or Nm

Probable genotypes
here are either NN
or Nm
Let NN-represents for the homozygous dominant for normal
Nn-heterozygous carrier for the recessive allele- does not show the disorder
nn-homozygous recessive allele-affected/shows the disorder

In this pedigree, I can say that this is not a sex-linked since both male and female are affected by
this disorder. This is not due to the defective part on the X or Y sex chromosomes. So I came up to a
conclusion that this is an autosomal recessive disorder. For a person to be affected by this disorder
he/she must have the two recessive alleles. In the first generation, we can see that the father on the left
is afflicted with the disorder and married to a normal female. It was shown that there are no offspring
who inherited or manifested the disorder. On the other hand, on the right portion, two phenotypically
normal persons have an offspring that bear or manifested the disorder. It is interesting to note why they
are able to produce an offspring who is myopic when the two are normal. From this, we can conclude
that the two parents are carrier for the disorder. That’s why we represented it with Nn for the alleles of
the two parents who are carrier for the trait. So in that cross, we can produce one recessive allele and
three dominant alleles, but we can’t determine whose in the pedigree who will receive the exact trait
for that allele except for the affected one with nn. In the second generation, their child were married to
each other and they are able to produce a female offspring who are myopic. In this sense, both the
parents here are carrier that’s why we assign Nn on the father and mother so we can expect that they
will bear a child who is nn in the third generation. It is now clear that this disorder is inherited as the
result of a recessive trait.

C. REAL PROBLEM PROBLEMS

Answer the following problems and show your solution/explanation. (20 points)

1. Albinism in humans is inherited as a simple recessive trait. For the following families, determine
the genotypes of the parents and offspring. (When two alternative genotypes are possible, list
both).
a. Two normal parents have 5 children, four normal and one albino

Answer: Parent genotypes: Both parents must be heterozygous dominant-both must be Aa.
Offspring genotypes: Normal children must be AA, Aa.
Albino child must be aa.

b. A normal male and an albino female have six children, all normal

Answer: Parent genotypes: Father must be homozygous dominant AA.

Mother who is albino must be aa.
Offspring genotypes: Normal children must be Aa.
 c. A normal male and an albino female have six children, three normal, three albino

Answer: Parent genotypes: Father must be heterozygous dominant Aa.

Mother who is albino must be aa.
Offspring genotypes: Normal children must be Aa.
Albino children must be aa.

d. Construct a pedigree of the families in (b) and (c). Assume that one of the normal children in
(b) and one of the albino children in (c) become the parents of eight children. Add these
children to the pedigree, and predict their phenotypes (albino or nomal)

PEDIGREE SOLUTIONS
Family B Family C
 50%- albino either male/female
50%- normal either male/female

Since we assumed that one of the normal children in (b) and one of the albino children in (c) become the
parents of eight children. We will be predicting the expected phenotypes in the third generation.

Solutions:

Based on the illustration, a cross between a heterozygous male (Aa) who is normal but bearer of
the recessive allele for albinism and a woman who is homozygous recessive for albinism (aa) resulted to
50-50 chance of having a normal and albino offspring. In this case, 4 offspring either male or female will
be normal and 4 offspring either male or female will have the disorder/albinism.
2. How many different types of gametes can be formed by individuals of the following genotypes:
a. AaBb b. AaBB c. AaBbCc d. AaBBcc and e. AaBBcc

What are the gametes in each case?

a. AaBb- produces 4 types of gametes (AB, Ab, aB, ab)

b. AaBbCc- produces 2 types of gametes (AB, Ab)

c. AaBbCc - produces 8 types of gametes (ABC, ABc, AbC, Abc, aBC, aBc, abC, abc)

d. AaBBcc - produces 4 types of gametes (ABC, ABc, aBC, aBc)

 e. AaBBcc - produces 2 types of gametes (ABc, aBc)

D. EXPLORING GENOMICS
Refer to the attached word document on Exploring Genomics. Do exercise 1 and 2. (20 points)

Exercise I:

a. Which gene is mutated in individuals with sickle-cell anemia?

b. What are the major symptoms of this disorder?
c. What was the first published scientific description of sickle-cell anemia?
d. Describe two other features of this disorder that you learned from the OMIM database, and
state where in the database you found the information.

Answers:

a. Sickle cell anemia  is the result of mutant beta globin (HBB; 141900) in which the mutation
causes sickling of hemoglobin.  The gene for beta globin is mutated.

b. Sickle cell anemia   is a multisystem disease associated with episodes of acute illness and
progressive organ damage. Other literature mentioned some of the symptoms of the disorder
which can vary considerably from person to person like pain develops when sickle-shaped red
blood cells block the flow of blood to the chest, abdomen and joints. Some Symptoms can have
a significant impact on quality of life and can lead to life-threatening complications such as
stroke where the supply of blood to the brain becomes blocked; acute chest syndrome where
the lungs suddenly lose their ability to breathe in oxygen as a result of sickle cells blocking blood
vessels in the lungs; increased risk of infection where sickle cell anemia can damage the spleen,
a key organ involved in fighting infection; pulmonary hypertension where sickle-shaped red
 blood cells block the flow of blood from the heart to the lungs causing the blood pressure in
these vessels to become dangerously high.

c. The first description of sickle cell disease was by a Chicago physician, James B. Herrick, who
noted in 1910 that a patient of his from the West Indies had an anemia characterized by unusual
red cells that were "sickle shaped. The disorder we call “Sickle Cell Disease” often abbreviated as
SCD, had been present in Africa for at least five thousand years and has been known by many
names in many tribal languages. What we call its “discovery” in 1910 occurred, not in Africa, but
in the United States. A young man named Walter Clement Noel from the island of Grenada, a
dental student studying in Chicago, went to Dr. James B. Herrick with complaints of pain
episodes, and symptoms of anemia. Herrick was a cardiologist and not too interested in Noel’s
case so he assigned a resident, Dr. Ernest Irons to the case. Irons examined Noel’s blood under
the microscope and saw red blood cells he described as “having the shape of a sickle”. When
Herrick saw this in the chart, he became interested because he saw that this might be a new,
unknown, disease. He subsequently published a paper in one of the medical journals in which he
used the term “sickle shaped cells”.

d. Other features that I learned from the search in OMIM database about sickle cell anemia
are:
Link: *141900
1. The alpha (HBA1, 141800; HBA2, 141850) and beta (HBB) loci determine the structure of the 2
types of polypeptide chains in adult hemoglobin, HbA. Mutant beta globin that sickles causes
sickle cell anemia(603903). Absence of beta chain causes beta-zero-thalassemia. Reduced
amounts of detectable beta globin causes beta-plus-thalassemia.Use of a combination of
somatic cell hybridization and hybridization of DNA probes permitted assignment of the beta
hemoglobin locus to chromosome 11 (Deisseroth et al., 1978). Parallel experiments showed that
the gamma globin genes (HBG1, 142200; HBG2, 142250) are also on chromosome 11, a result to
be expected from other data indicating linkage of beta and gamma.
Another interesting to note based from my readings in this link is that rapid detection of
the sickle cell mutation is possible by amplifying the region of codon 6 by PCR and digesting the
amplification product by a restriction endonuclease whose recognition site is abolished by the A-
to-T mutation, the resulting abnormal fragment being detected with ethidium bromide staining
after electrophoresis. Detection of the HbC mutation is more difficult since no known restriction-
endonuclease site is abolished or created by the mutation. Fischel-Ghodsian et al.
(1990) described a rapid allele-specific PCR amplification technique that allowed detection of
the HbC mutation in an even shorter time span than the one required for detecting the HbS
mutation (141900.0243).
2. In the study of the causes and outcomes of the acute chest syndrome in sickle cell disease by
the National Acute Chest Syndrome Study Group. They found out that among patients with
sickle cell disease, the acute chest syndrome is commonly precipitated by fat embolism and
infection, especially community-acquired pneumonia. Among older patients and those with
neurologic symptoms, the syndrome often progresses to respiratory failure. Treatment with
 transfusions and bronchodilators improves oxygenation, and with aggressive treatment, most
patients who have respiratory failure recover.

Source: Vichinsky, E. P., Neumayr, L. D., Earles, A. N., Williams, R., Lennette, E. T., Dean, D., Nickerson, B.,
Orringer, E., McKie, V., Bellevue, R., Daeschner, C., Manci, E. A. Causes and outcomes of the acute chest
syndrome in sickle cell disease. New Eng. J. Med. 342: 1855-1865, 2000. Note: Erratum: New Eng. J. Med.
343: 824 only, 2000. [PubMed: 10861320, related citations] 

Exercise II:

Select another human disorder that is inherited as either a dominant or recessive trait and
investigate its features, following the general steps described in Exercise I. Follow links from OMIM to
other databases if you choose. Describe several interesting pieces of information you acquired during
your exploration and cite the information sources you encountered during the search.

Link: # 306900. HEMOPHILIA B; HEMB

a. Hemophila B, also known as Christmas disease, is caused by mutation in the gene encoding
coagulation factor IX (F9; 300746). Mutation in the F9 gene. Hemophilia B due to factor IX
deficiency is phenotypically indistinguishable from hemophilia A (306700), which results from
deficiency of coagulation factor VIII (F8; 300841). The classic laboratory findings in hemophilia B
include a prolonged activated partial thromboplastin time (aPTT) and a normal prothrombin
time (PT). Hemophilia B is classically transmitted as an X-linked recessive disorder. Cutler et al.
(2004) described a family in which the usual pattern of X-linked inheritance of hemophilia B was
complicated by mosaicism in the proband's maternal grandfather. The proband was a male
infant with severe factor IX deficiency who was initially thought to be a sporadic case. Testing of
other family members identified his mother as a carrier and his asymptomatic maternal
grandfather as having very mild factor IX deficiency. The causative mutation was identified as a
2-bp deletion (AG within codons 134-135) in the F9 gene (300746.0110)
b. Symptoms includes Chronic synovitis which occurs in patients with severe hemophilia. Chronic
synovitis presented as swelling of the joint with heat and redness and absence of response to
treatment with factor concentrate. Other Symptoms may include: bleeding into joints with
associated pain and swelling, blood in the urine or stool, bruising, gastrointestinal tract and
urinary tract bleeding, nosebleeds, prolonged bleeding from cuts, tooth extraction, and surgery
and bleeding that starts without cause.
c. In 1803, John Conrad Otto, a Philadelphia physician, was the first to publish an article
recognizing that a hemorrhagic bleeding disorder primarily affected men, and ran in certain
families. He traced the disease back to a female ancestor living in Plymouth, New Hampshire, in
1720. Otto called the males “bleeders.” In 1813, John Hay published a paper in the New England
Journal of Medicine proposing that affected men could pass the trait for a bleeding disorder to
their unaffected daughters. Then in 1828, Friedrich Hopff, a student at the University of Zurich,
and his professor Dr. Schonlein, are credited with coining the term “haemorrhaphilia” for the
condition, later shorted to “haemophilia.”
d. Other features that I learned from the search in OMIM database about hemophila B are:
1. Veltkamp et al. (1970) described a variant of hemophilia B termed hemophilia B Leyden, in a
Dutch family. The disorder was characterized by the disappearance of the bleeding diathesis
 as the patient aged. In affected individuals, plasma factor IX levels were less than 1% of
normal before puberty, but after puberty factor IX activity and antigen levels rose steadily in
a 1:1 ratio to a maximum of 50 to 60%. In affected members of 2 Dutch pedigrees with
hemophilia B Leyden, Reitsma et al. (1988) found that patients with hemophilia B Leyden
had a mutation in the promoter region of the F9 gene (300746.0001). The findings
suggested that a point mutation could lead to a switch from constitutive to steroid
hormone-dependent gene expression. The families were probably related.

Source: Veltkamp, J. J., Meilof, J., Remmelts, H. G., Van der Vlerk, D., Loeliger, E. A.  Another genetic
variant of hemophilia B:haemophilia B Leyden. Scand. J. Haemat. 7: 82-90, 1970.
[PubMed: 5450691, related citations]/ https://pubmed.ncbi.nlm.nih.gov/5450691/

2. A wide range of factor VIII and IX levels is observed in heterozygous carriers of hemophilia as
well as in noncarriers. In female carriers, extreme lyonization may lead to low clotting factor
levels. They studied the effect of heterozygous hemophilia carriership on the occurrence of
bleeding symptoms. A postal survey was performed among most of the women who were
tested for carriership of hemophilia in the Netherlands before 2001. The questionnaire
included items on personal characteristics, characteristics of hemophilia in the affected
family members, and carrier testing and history of bleeding problems such as bleeding after
tooth extraction, bleeding after tonsillectomy, and other operations. Information on clotting
factor levels was obtained from the hospital charts. Logistic regression was used to assess
the relation of carrier status and clotting factor levels with the occurrence of hemorrhagic
events. In 2004, 766 questionnaires were sent, and 546 women responded (80%). Of these,
274 were carriers of hemophilia A or B. The median clotting factor level of carriers was 0.60
IU/mL (range, 0.05-2.19 IU/mL) compared with 1.02 IU/mL (range, 0.45-3.28 IU/mL) in
noncarriers. Clotting factor levels from 0.60 to 0.05 IU/mL were increasingly associated with
prolonged bleeding from small wounds and prolonged bleeding after tooth extraction,
tonsillectomy, and operations. Carriers of hemophilia bleed more than other women,
especially after medical interventions. Their findings suggest that not only clotting factor
levels at the extreme of the distribution, resembling mild hemophilia, but also mildly
reduced clotting factor levels between 0.41 and 0.60 IU/mL are associated with bleeding.

Source: Plug, I., Mauser-Bunschoten, E. P., Brocker-Vriends, A. H. J. T., van Amstel, H. K. P.,
van der Bom, J. G., van Diemen-Homan, J. E. M., Willemse, J., Rosendaal, F. R. Bleeding in
carriers of hemophilia. Blood 108: 52-56, 2006. [PubMed: 16551972, related citations]/
https://pubmed.ncbi.nlm.nih.gov/16551972/